what is a central thesis

Walden University
Faculty Portal

Writing a Paper: Thesis Statements

Basics of thesis statements.

The thesis statement is the brief articulation of your paper's central argument and purpose. You might hear it referred to as simply a "thesis." Every scholarly paper should have a thesis statement, and strong thesis statements are concise, specific, and arguable. Concise means the thesis is short: perhaps one or two sentences for a shorter paper. Specific means the thesis deals with a narrow and focused topic, appropriate to the paper's length. Arguable means that a scholar in your field could disagree (or perhaps already has!).

Strong thesis statements address specific intellectual questions, have clear positions, and use a structure that reflects the overall structure of the paper. Read on to learn more about constructing a strong thesis statement.

Being Specific

This thesis statement has no specific argument:

Needs Improvement: In this essay, I will examine two scholarly articles to find similarities and differences.

This statement is concise, but it is neither specific nor arguable—a reader might wonder, "Which scholarly articles? What is the topic of this paper? What field is the author writing in?" Additionally, the purpose of the paper—to "examine…to find similarities and differences" is not of a scholarly level. Identifying similarities and differences is a good first step, but strong academic argument goes further, analyzing what those similarities and differences might mean or imply.

Better: In this essay, I will argue that Bowler's (2003) autocratic management style, when coupled with Smith's (2007) theory of social cognition, can reduce the expenses associated with employee turnover.

The new revision here is still concise, as well as specific and arguable. We can see that it is specific because the writer is mentioning (a) concrete ideas and (b) exact authors. We can also gather the field (business) and the topic (management and employee turnover). The statement is arguable because the student goes beyond merely comparing; he or she draws conclusions from that comparison ("can reduce the expenses associated with employee turnover").

Making a Unique Argument

This thesis draft repeats the language of the writing prompt without making a unique argument:

Needs Improvement: The purpose of this essay is to monitor, assess, and evaluate an educational program for its strengths and weaknesses. Then, I will provide suggestions for improvement.

You can see here that the student has simply stated the paper's assignment, without articulating specifically how he or she will address it. The student can correct this error simply by phrasing the thesis statement as a specific answer to the assignment prompt.

Better: Through a series of student interviews, I found that Kennedy High School's antibullying program was ineffective. In order to address issues of conflict between students, I argue that Kennedy High School should embrace policies outlined by the California Department of Education (2010).

Words like "ineffective" and "argue" show here that the student has clearly thought through the assignment and analyzed the material; he or she is putting forth a specific and debatable position. The concrete information ("student interviews," "antibullying") further prepares the reader for the body of the paper and demonstrates how the student has addressed the assignment prompt without just restating that language.

Creating a Debate

This thesis statement includes only obvious fact or plot summary instead of argument:

Needs Improvement: Leadership is an important quality in nurse educators.

A good strategy to determine if your thesis statement is too broad (and therefore, not arguable) is to ask yourself, "Would a scholar in my field disagree with this point?" Here, we can see easily that no scholar is likely to argue that leadership is an unimportant quality in nurse educators. The student needs to come up with a more arguable claim, and probably a narrower one; remember that a short paper needs a more focused topic than a dissertation.

Better: Roderick's (2009) theory of participatory leadership is particularly appropriate to nurse educators working within the emergency medicine field, where students benefit most from collegial and kinesthetic learning.

Here, the student has identified a particular type of leadership ("participatory leadership"), narrowing the topic, and has made an arguable claim (this type of leadership is "appropriate" to a specific type of nurse educator). Conceivably, a scholar in the nursing field might disagree with this approach. The student's paper can now proceed, providing specific pieces of evidence to support the arguable central claim.

Choosing the Right Words

This thesis statement uses large or scholarly-sounding words that have no real substance:

Needs Improvement: Scholars should work to seize metacognitive outcomes by harnessing discipline-based networks to empower collaborative infrastructures.

There are many words in this sentence that may be buzzwords in the student's field or key terms taken from other texts, but together they do not communicate a clear, specific meaning. Sometimes students think scholarly writing means constructing complex sentences using special language, but actually it's usually a stronger choice to write clear, simple sentences. When in doubt, remember that your ideas should be complex, not your sentence structure.

Better: Ecologists should work to educate the U.S. public on conservation methods by making use of local and national green organizations to create a widespread communication plan.

Notice in the revision that the field is now clear (ecology), and the language has been made much more field-specific ("conservation methods," "green organizations"), so the reader is able to see concretely the ideas the student is communicating.

Leaving Room for Discussion

This thesis statement is not capable of development or advancement in the paper:

Needs Improvement: There are always alternatives to illegal drug use.

This sample thesis statement makes a claim, but it is not a claim that will sustain extended discussion. This claim is the type of claim that might be appropriate for the conclusion of a paper, but in the beginning of the paper, the student is left with nowhere to go. What further points can be made? If there are "always alternatives" to the problem the student is identifying, then why bother developing a paper around that claim? Ideally, a thesis statement should be complex enough to explore over the length of the entire paper.

Better: The most effective treatment plan for methamphetamine addiction may be a combination of pharmacological and cognitive therapy, as argued by Baker (2008), Smith (2009), and Xavier (2011).

In the revised thesis, you can see the student make a specific, debatable claim that has the potential to generate several pages' worth of discussion. When drafting a thesis statement, think about the questions your thesis statement will generate: What follow-up inquiries might a reader have? In the first example, there are almost no additional questions implied, but the revised example allows for a good deal more exploration.

Thesis Mad Libs

If you are having trouble getting started, try using the models below to generate a rough model of a thesis statement! These models are intended for drafting purposes only and should not appear in your final work.

In this essay, I argue ____, using ______ to assert _____.
While scholars have often argued ______, I argue______, because_______.
Through an analysis of ______, I argue ______, which is important because_______.

Words to Avoid and to Embrace

When drafting your thesis statement, avoid words like explore, investigate, learn, compile, summarize , and explain to describe the main purpose of your paper. These words imply a paper that summarizes or "reports," rather than synthesizing and analyzing.

Instead of the terms above, try words like argue, critique, question , and interrogate . These more analytical words may help you begin strongly, by articulating a specific, critical, scholarly position.

Read Kayla's blog post for tips on taking a stand in a well-crafted thesis statement.

Related Resources

Didn't find what you need? Search our website or email us .

Read our website accessibility and accommodation statement .

Previous Page: Introductions
Next Page: Conclusions
Office of Student Disability Services

Walden Resources

Departments.

Academic Residencies
Academic Skills
Career Planning and Development
Customer Care Team
Field Experience
Military Services
Student Success Advising
Writing Skills

Centers and Offices

Center for Social Change
Office of Academic Support and Instructional Services
Office of Degree Acceleration
Office of Research and Doctoral Services
Office of Student Affairs

Student Resources

Doctoral Writing Assessment
Form & Style Review
Quick Answers
ScholarWorks
SKIL Courses and Workshops
Walden Bookstore
Walden Catalog & Student Handbook
Student Safety/Title IX
Legal & Consumer Information
Website Terms and Conditions
Cookie Policy
Accessibility
Accreditation
State Authorization
Net Price Calculator
Contact Walden

Have a language expert improve your writing

Run a free plagiarism check in 10 minutes, generate accurate citations for free.

Knowledge Base
Dissertation
What Is a Thesis? | Ultimate Guide & Examples

What Is a Thesis? | Ultimate Guide & Examples

Published on September 14, 2022 by Tegan George . Revised on November 21, 2023.

A thesis is a type of research paper based on your original research. It is usually submitted as the final step of a master’s program or a capstone to a bachelor’s degree.

Writing a thesis can be a daunting experience. Other than a dissertation , it is one of the longest pieces of writing students typically complete. It relies on your ability to conduct research from start to finish: choosing a relevant topic , crafting a proposal , designing your research , collecting data , developing a robust analysis, drawing strong conclusions , and writing concisely .

Thesis template

You can also download our full thesis template in the format of your choice below. Our template includes a ready-made table of contents , as well as guidance for what each chapter should include. It’s easy to make it your own, and can help you get started.

Download Word template Download Google Docs template

Instantly correct all language mistakes in your text

Upload your document to correct all your mistakes in minutes

Thesis vs. thesis statement, how to structure a thesis, acknowledgements or preface, list of figures and tables, list of abbreviations, introduction, literature review, methodology, reference list, proofreading and editing, defending your thesis, other interesting articles, frequently asked questions about theses.

You may have heard the word thesis as a standalone term or as a component of academic writing called a thesis statement . Keep in mind that these are two very different things.

A thesis statement is a very common component of an essay, particularly in the humanities. It usually comprises 1 or 2 sentences in the introduction of your essay , and should clearly and concisely summarize the central points of your academic essay .
A thesis is a long-form piece of academic writing, often taking more than a full semester to complete. It is generally a degree requirement for Master’s programs, and is also sometimes required to complete a bachelor’s degree in liberal arts colleges.
In the US, a dissertation is generally written as a final step toward obtaining a PhD.
In other countries (particularly the UK), a dissertation is generally written at the bachelor’s or master’s level.

The only proofreading tool specialized in correcting academic writing - try for free!

The academic proofreading tool has been trained on 1000s of academic texts and by native English editors. Making it the most accurate and reliable proofreading tool for students.

Try for free

The final structure of your thesis depends on a variety of components, such as:

Your discipline
Your theoretical approach

Humanities theses are often structured more like a longer-form essay . Just like in an essay, you build an argument to support a central thesis.

In both hard and social sciences, theses typically include an introduction , literature review , methodology section , results section , discussion section , and conclusion section . These are each presented in their own dedicated section or chapter. In some cases, you might want to add an appendix .

Thesis examples

We’ve compiled a short list of thesis examples to help you get started.

Example thesis #1: “Abolition, Africans, and Abstraction: the Influence of the ‘Noble Savage’ on British and French Antislavery Thought, 1787-1807” by Suchait Kahlon.
Example thesis #2: “’A Starving Man Helping Another Starving Man’: UNRRA, India, and the Genesis of Global Relief, 1943-1947″ by Julian Saint Reiman.

The very first page of your thesis contains all necessary identifying information, including:

Your full title
Your full name
Your department
Your institution and degree program
Your submission date.

Sometimes the title page also includes your student ID, the name of your supervisor, or the university’s logo. Check out your university’s guidelines if you’re not sure.

Receive feedback on language, structure, and formatting

Professional editors proofread and edit your paper by focusing on:

Academic style
Vague sentences
Style consistency

See an example

An abstract is a short summary of your thesis. Usually a maximum of 300 words long, it’s should include brief descriptions of your research objectives , methods, results, and conclusions. Though it may seem short, it introduces your work to your audience, serving as a first impression of your thesis.

Theoretical framework

Your literature review can often form the basis for your theoretical framework, but these are not the same thing. A theoretical framework defines and analyzes the concepts and theories that your research hinges on.

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the “Cite this Scribbr article” button to automatically add the citation to our free Citation Generator.

George, T. (2023, November 21). What Is a Thesis? | Ultimate Guide & Examples. Scribbr. Retrieved April 2, 2024, from https://www.scribbr.com/dissertation/thesis/

Is this article helpful?

Tegan George

Other students also liked, dissertation & thesis outline | example & free templates, writing strong research questions | criteria & examples, 10 research question examples to guide your research project, "i thought ai proofreading was useless but..".

I've been using Scribbr for years now and I know it's a service that won't disappoint. It does a good job spotting mistakes”

You can turn a subject into a central idea by focusing. Begin by reviewing what you know about your subject or by looking over notes you have made about it through listing, brainstorming, clustering, freewriting, or other prewriting activities.

With these details fresh in your mind, ask yourself:

What is my purpose in writing about this topic? What main point do I want to make about the topic?

WHAT IS MY PURPOSE?

Let's say you decide to write about high school. You might tell a story about your history class, compare two schools you attended, or argue that high schools should require foreign-language study.

If you want to compare the two high schools you attended, you can include details about their academic programs, athletic teams, students, or teachers. But you probably wouldn't argue that high schools should stay open in summer because doing so would take you outside your declared purpose.

WHAT IS MY MAIN POINT?

The next step in focusing is to decide what to say about your subject. What is the most interesting or important point you want to make about the schools you are comparing? The answer will be your main point, which ties all the details of the essay together.

Again, you turn an abstract subject into a central idea by stating a main point about that subject. If your main point is that entering a new school improved your attitude about education, your central idea might read:

Changing high schools made me a more serious student.

MAKING A POINT ABOUT A SUBJECT

In the box below, main points have been added to subjects to form working topic sentences or thesis statements.

CHECK YOUR WORKING CENTRAL IDEA

After writing a working central idea, check it for qualities that will make it effective as the basis of a paragraph or essay. Ask yourself:

Is my central idea expressed in a complete thought? Is it specific? Does it express an idea that is worth developing in a full-length paragraph or essay? Is it limited enough to discuss in a short piece of writing?

Never confuse a central idea with a simple subject. Central ideas are expressed in complete sentences; subjects are words or phrases. Take these subjects:

The city zoo. Professional athletes. Majoring in foreign languages.

Can you write a paragraph or essay on one of these subjects? Only if you decide on the main point you want to make about it. Try these as working central ideas:

The city zoo is in great need of repairs. Professional athletes are overpaid. Studying foreign languages leads to many career choices.

A CENTRAL IDEA IS SPECIFIC

Make your central idea specific. The key to this step is to focus your main point as precisely as you can. That will give you a clear direction to follow as you develop an essay or paragraph. Take this central idea:

Jogging isn't for everybody.

It is correct, but it leaves questions unanswered. For example, what kind of people should not jog? What ill effects might jogging cause them? Now, try this:

Jogging can be harmful to people who suffer from heart, back, or joint problems.

A CENTRAL IDEA CONTAINS A MAIN POINT THAT IS WORTH DEVELOPING

Make sure your main point is an idea-not just a fact-that is worth developing in a full-length paragraph or essay. Read these two sentences:

The War Memorial is in Ottawa. The War Memorial has been severely vandalized.

The first sentence is a statement of fact; it does not call for discussion. The second lends itself to discussion. For example, you might describe what the vandals did, explain how much repairs will cost, or discuss ways to prevent future problems.

A CENTRAL IDEA IS LIMITED

Essays that beginning college or university students write usually contain approximately five to seven paragraphs of about 50 to 100 words. Therefore, you should limit your working topic sentence or thesis, making it as specific as you can. Otherwise, you won't be able to make your point clearly and completely.

LIMIT THE DISCUSSION TO A MANAGEABLE LENGTH

Let's say you want to convince someone to stop smoking. You might limit yourself to three reasons to stop smoking: the health risks, the costs, and its effects on others.

Here's your working thesis:

Break the habit: otherwise, it will ruin your health, empty your wallet, and annoy your friends.

Your working topic sentences, which will control the three body paragraphs, could be as follows:

Smoking causes cancer, emphysema, and heart disease. You can save hundreds or even thousands of dollars a year by quitting. Smoking is offensive to friends and family.

LIMITING YOUR CENTRAL IDEA FURTHER

You begin a rough draft by discussing illnesses caused by smoking. However, you soon realize that you can't cover all three reasons for quitting and still keep the essay short. So you limit yourself to the issue of health risks.

Your thesis statement becomes:

Break the habit: smoking causes heart disease, emphysema, and cancer.

Your topic sentences become:

Smoking weakens the heart and impairs circulation. Smoking is a major cause of emphysema. Smoking has been linked directly to cancer of the mouth and the esophagus.

DIFFERENCES BETWEEN A TOPIC SENTENCE AND A THESIS

A topic sentence is the sentence that expresses the central idea of a paragraph. A thesis statement is a sentence that expresses the central idea of an essay.

It's a good idea to decide the topic sentence of a paragraph after writing the working version of an essay's thesis. A topic sentence explains one aspect or point in the thesis and, therefore, should always be more specific and limited than a thesis.

REVISE AND REFINE THE CENTRAL IDEA AS YOU WORK

You can revise a central idea whenever you need to. The working version of a topic sentence or thesis statement provides only a starting point and a sense of direction. Don't be afraid to look back to your central ideas and rewrite them often. As a matter of fact, focusing is something you should do throughout the writing process.

The Writing Center • University of North Carolina at Chapel Hill

Thesis Statements

What this handout is about.

This handout describes what a thesis statement is, how thesis statements work in your writing, and how you can craft or refine one for your draft.

Introduction

Writing in college often takes the form of persuasion—convincing others that you have an interesting, logical point of view on the subject you are studying. Persuasion is a skill you practice regularly in your daily life. You persuade your roommate to clean up, your parents to let you borrow the car, your friend to vote for your favorite candidate or policy. In college, course assignments often ask you to make a persuasive case in writing. You are asked to convince your reader of your point of view. This form of persuasion, often called academic argument, follows a predictable pattern in writing. After a brief introduction of your topic, you state your point of view on the topic directly and often in one sentence. This sentence is the thesis statement, and it serves as a summary of the argument you’ll make in the rest of your paper.

What is a thesis statement?

A thesis statement:

tells the reader how you will interpret the significance of the subject matter under discussion.
is a road map for the paper; in other words, it tells the reader what to expect from the rest of the paper.
directly answers the question asked of you. A thesis is an interpretation of a question or subject, not the subject itself. The subject, or topic, of an essay might be World War II or Moby Dick; a thesis must then offer a way to understand the war or the novel.
makes a claim that others might dispute.
is usually a single sentence near the beginning of your paper (most often, at the end of the first paragraph) that presents your argument to the reader. The rest of the paper, the body of the essay, gathers and organizes evidence that will persuade the reader of the logic of your interpretation.

If your assignment asks you to take a position or develop a claim about a subject, you may need to convey that position or claim in a thesis statement near the beginning of your draft. The assignment may not explicitly state that you need a thesis statement because your instructor may assume you will include one. When in doubt, ask your instructor if the assignment requires a thesis statement. When an assignment asks you to analyze, to interpret, to compare and contrast, to demonstrate cause and effect, or to take a stand on an issue, it is likely that you are being asked to develop a thesis and to support it persuasively. (Check out our handout on understanding assignments for more information.)

How do I create a thesis?

Writers use all kinds of techniques to stimulate their thinking and to help them clarify relationships or comprehend the broader significance of a topic and arrive at a thesis statement. For more ideas on how to get started, see our handout on brainstorming .

How do I know if my thesis is strong?

If there’s time, run it by your instructor or make an appointment at the Writing Center to get some feedback. Even if you do not have time to get advice elsewhere, you can do some thesis evaluation of your own. When reviewing your first draft and its working thesis, ask yourself the following :

Do I answer the question? Re-reading the question prompt after constructing a working thesis can help you fix an argument that misses the focus of the question. If the prompt isn’t phrased as a question, try to rephrase it. For example, “Discuss the effect of X on Y” can be rephrased as “What is the effect of X on Y?”
Have I taken a position that others might challenge or oppose? If your thesis simply states facts that no one would, or even could, disagree with, it’s possible that you are simply providing a summary, rather than making an argument.
Is my thesis statement specific enough? Thesis statements that are too vague often do not have a strong argument. If your thesis contains words like “good” or “successful,” see if you could be more specific: why is something “good”; what specifically makes something “successful”?
Does my thesis pass the “So what?” test? If a reader’s first response is likely to be “So what?” then you need to clarify, to forge a relationship, or to connect to a larger issue.
Does my essay support my thesis specifically and without wandering? If your thesis and the body of your essay do not seem to go together, one of them has to change. It’s okay to change your working thesis to reflect things you have figured out in the course of writing your paper. Remember, always reassess and revise your writing as necessary.
Does my thesis pass the “how and why?” test? If a reader’s first response is “how?” or “why?” your thesis may be too open-ended and lack guidance for the reader. See what you can add to give the reader a better take on your position right from the beginning.

Suppose you are taking a course on contemporary communication, and the instructor hands out the following essay assignment: “Discuss the impact of social media on public awareness.” Looking back at your notes, you might start with this working thesis:

Social media impacts public awareness in both positive and negative ways.

You can use the questions above to help you revise this general statement into a stronger thesis.

Do I answer the question? You can analyze this if you rephrase “discuss the impact” as “what is the impact?” This way, you can see that you’ve answered the question only very generally with the vague “positive and negative ways.”
Have I taken a position that others might challenge or oppose? Not likely. Only people who maintain that social media has a solely positive or solely negative impact could disagree.
Is my thesis statement specific enough? No. What are the positive effects? What are the negative effects?
Does my thesis pass the “how and why?” test? No. Why are they positive? How are they positive? What are their causes? Why are they negative? How are they negative? What are their causes?
Does my thesis pass the “So what?” test? No. Why should anyone care about the positive and/or negative impact of social media?

After thinking about your answers to these questions, you decide to focus on the one impact you feel strongly about and have strong evidence for:

Because not every voice on social media is reliable, people have become much more critical consumers of information, and thus, more informed voters.

This version is a much stronger thesis! It answers the question, takes a specific position that others can challenge, and it gives a sense of why it matters.

Let’s try another. Suppose your literature professor hands out the following assignment in a class on the American novel: Write an analysis of some aspect of Mark Twain’s novel Huckleberry Finn. “This will be easy,” you think. “I loved Huckleberry Finn!” You grab a pad of paper and write:

Mark Twain’s Huckleberry Finn is a great American novel.

You begin to analyze your thesis:

Do I answer the question? No. The prompt asks you to analyze some aspect of the novel. Your working thesis is a statement of general appreciation for the entire novel.

Think about aspects of the novel that are important to its structure or meaning—for example, the role of storytelling, the contrasting scenes between the shore and the river, or the relationships between adults and children. Now you write:

In Huckleberry Finn, Mark Twain develops a contrast between life on the river and life on the shore.

Do I answer the question? Yes!
Have I taken a position that others might challenge or oppose? Not really. This contrast is well-known and accepted.
Is my thesis statement specific enough? It’s getting there–you have highlighted an important aspect of the novel for investigation. However, it’s still not clear what your analysis will reveal.
Does my thesis pass the “how and why?” test? Not yet. Compare scenes from the book and see what you discover. Free write, make lists, jot down Huck’s actions and reactions and anything else that seems interesting.
Does my thesis pass the “So what?” test? What’s the point of this contrast? What does it signify?”

After examining the evidence and considering your own insights, you write:

Through its contrasting river and shore scenes, Twain’s Huckleberry Finn suggests that to find the true expression of American democratic ideals, one must leave “civilized” society and go back to nature.

This final thesis statement presents an interpretation of a literary work based on an analysis of its content. Of course, for the essay itself to be successful, you must now present evidence from the novel that will convince the reader of your interpretation.

Works consulted

We consulted these works while writing this handout. This is not a comprehensive list of resources on the handout’s topic, and we encourage you to do your own research to find additional publications. Please do not use this list as a model for the format of your own reference list, as it may not match the citation style you are using. For guidance on formatting citations, please see the UNC Libraries citation tutorial . We revise these tips periodically and welcome feedback.

Anson, Chris M., and Robert A. Schwegler. 2010. The Longman Handbook for Writers and Readers , 6th ed. New York: Longman.

Lunsford, Andrea A. 2015. The St. Martin’s Handbook , 8th ed. Boston: Bedford/St Martin’s.

Ramage, John D., John C. Bean, and June Johnson. 2018. The Allyn & Bacon Guide to Writing , 8th ed. New York: Pearson.

Ruszkiewicz, John J., Christy Friend, Daniel Seward, and Maxine Hairston. 2010. The Scott, Foresman Handbook for Writers , 9th ed. Boston: Pearson Education.

You may reproduce it for non-commercial use if you use the entire handout and attribute the source: The Writing Center, University of North Carolina at Chapel Hill

Make a Gift

How to Write a Solid Thesis Statement

The important sentence expresses your central assertion or argument

arabianEye / Getty Images

Writing Research Papers
Writing Essays
English Grammar
M.Ed., Education Administration, University of Georgia
B.A., History, Armstrong State University

A thesis statement provides the foundation for your entire research paper or essay. This statement is the central assertion that you want to express in your essay. A successful thesis statement is one that is made up of one or two sentences clearly laying out your central idea and expressing an informed, reasoned answer to your research question.

Usually, the thesis statement will appear at the end of the first paragraph of your paper. There are a few different types, and the content of your thesis statement will depend upon the type of paper you’re writing.

Key Takeaways: Writing a Thesis Statement

A thesis statement gives your reader a preview of your paper's content by laying out your central idea and expressing an informed, reasoned answer to your research question.
Thesis statements will vary depending on the type of paper you are writing, such as an expository essay, argument paper, or analytical essay.
Before creating a thesis statement, determine whether you are defending a stance, giving an overview of an event, object, or process, or analyzing your subject

Expository Essay Thesis Statement Examples

An expository essay "exposes" the reader to a new topic; it informs the reader with details, descriptions, or explanations of a subject. If you are writing an expository essay , your thesis statement should explain to the reader what she will learn in your essay. For example:

The United States spends more money on its military budget than all the industrialized nations combined.
Gun-related homicides and suicides are increasing after years of decline.
Hate crimes have increased three years in a row, according to the FBI.
Post-traumatic stress disorder (PTSD) increases the risk of stroke and arterial fibrillation (irregular heartbeat).

These statements provide a statement of fact about the topic (not just opinion) but leave the door open for you to elaborate with plenty of details. In an expository essay, you don't need to develop an argument or prove anything; you only need to understand your topic and present it in a logical manner. A good thesis statement in an expository essay always leaves the reader wanting more details.

Types of Thesis Statements

Before creating a thesis statement, it's important to ask a few basic questions, which will help you determine the kind of essay or paper you plan to create:

Are you defending a stance in a controversial essay ?
Are you simply giving an overview or describing an event, object, or process?
Are you conducting an analysis of an event, object, or process?

In every thesis statement , you will give the reader a preview of your paper's content, but the message will differ a little depending on the essay type .

Argument Thesis Statement Examples

If you have been instructed to take a stance on one side of a controversial issue, you will need to write an argument essay . Your thesis statement should express the stance you are taking and may give the reader a preview or a hint of your evidence. The thesis of an argument essay could look something like the following:

Self-driving cars are too dangerous and should be banned from the roadways.
The exploration of outer space is a waste of money; instead, funds should go toward solving issues on Earth, such as poverty, hunger, global warming, and traffic congestion.
The U.S. must crack down on illegal immigration.
Street cameras and street-view maps have led to a total loss of privacy in the United States and elsewhere.

These thesis statements are effective because they offer opinions that can be supported by evidence. If you are writing an argument essay, you can craft your own thesis around the structure of the statements above.

Analytical Essay Thesis Statement Examples

In an analytical essay assignment, you will be expected to break down a topic, process, or object in order to observe and analyze your subject piece by piece. Examples of a thesis statement for an analytical essay include:

The criminal justice reform bill passed by the U.S. Senate in late 2018 (" The First Step Act ") aims to reduce prison sentences that disproportionately fall on nonwhite criminal defendants.
The rise in populism and nationalism in the U.S. and European democracies has coincided with the decline of moderate and centrist parties that have dominated since WWII.
Later-start school days increase student success for a variety of reasons.

Because the role of the thesis statement is to state the central message of your entire paper, it is important to revisit (and maybe rewrite) your thesis statement after the paper is written. In fact, it is quite normal for your message to change as you construct your paper.

How to Write a Good Thesis Statement
What Is Expository Writing?
An Introduction to Academic Writing
Definition and Examples of Analysis in Composition
Write an Attention-Grabbing Opening Sentence for an Essay
How To Write an Essay
Tips on How to Write an Argumentative Essay
How to Write a Response Paper
The Ultimate Guide to the 5-Paragraph Essay
Understanding What an Expository Essay Is
The Introductory Paragraph: Start Your Paper Off Right
Tips for Writing an Art History Paper
How to Write a Persuasive Essay
The Five Steps of Writing an Essay
What an Essay Is and How to Write One
Development in Composition: Building an Essay

Resources Home 🏠
Try SciSpace Copilot
Search research papers
Add Copilot Extension
Try AI Detector
Try Paraphraser
Try Citation Generator
April Papers
June Papers
July Papers

What is a thesis | A Complete Guide with Examples

A thesis is a comprehensive academic paper based on your original research that presents new findings, arguments, and ideas of your study. It’s typically submitted at the end of your master’s degree or as a capstone of your bachelor’s degree.

However, writing a thesis can be laborious, especially for beginners. From the initial challenge of pinpointing a compelling research topic to organizing and presenting findings, the process is filled with potential pitfalls.

Therefore, to help you, this guide talks about what is a thesis. Additionally, it offers revelations and methodologies to transform it from an overwhelming task to a manageable and rewarding academic milestone.

What is a thesis?

A thesis is an in-depth research study that identifies a particular topic of inquiry and presents a clear argument or perspective about that topic using evidence and logic.

Writing a thesis showcases your ability of critical thinking, gathering evidence, and making a compelling argument. Integral to these competencies is thorough research, which not only fortifies your propositions but also confers credibility to your entire study.

Furthermore, there's another phenomenon you might often confuse with the thesis: the ' working thesis .' However, they aren't similar and shouldn't be used interchangeably.

A working thesis, often referred to as a preliminary or tentative thesis, is an initial version of your thesis statement. It serves as a draft or a starting point that guides your research in its early stages.

As you research more and gather more evidence, your initial thesis (aka working thesis) might change. It's like a starting point that can be adjusted as you learn more. It's normal for your main topic to change a few times before you finalize it.

While a thesis identifies and provides an overarching argument, the key to clearly communicating the central point of that argument lies in writing a strong thesis statement.

What is a thesis statement?

A strong thesis statement (aka thesis sentence) is a concise summary of the main argument or claim of the paper. It serves as a critical anchor in any academic work, succinctly encapsulating the primary argument or main idea of the entire paper.

Typically found within the introductory section, a strong thesis statement acts as a roadmap of your thesis, directing readers through your arguments and findings. By delineating the core focus of your investigation, it offers readers an immediate understanding of the context and the gravity of your study.

Furthermore, an effectively crafted thesis statement can set forth the boundaries of your research, helping readers anticipate the specific areas of inquiry you are addressing.

Different types of thesis statements

A good thesis statement is clear, specific, and arguable. Therefore, it is necessary for you to choose the right type of thesis statement for your academic papers.

Thesis statements can be classified based on their purpose and structure. Here are the primary types of thesis statements:

Argumentative (or Persuasive) thesis statement

Purpose : To convince the reader of a particular stance or point of view by presenting evidence and formulating a compelling argument.

Example : Reducing plastic use in daily life is essential for environmental health.

Analytical thesis statement

Purpose : To break down an idea or issue into its components and evaluate it.

Example : By examining the long-term effects, social implications, and economic impact of climate change, it becomes evident that immediate global action is necessary.

Expository (or Descriptive) thesis statement

Purpose : To explain a topic or subject to the reader.

Example : The Great Depression, spanning the 1930s, was a severe worldwide economic downturn triggered by a stock market crash, bank failures, and reduced consumer spending.

Cause and effect thesis statement

Purpose : To demonstrate a cause and its resulting effect.

Example : Overuse of smartphones can lead to impaired sleep patterns, reduced face-to-face social interactions, and increased levels of anxiety.

Compare and contrast thesis statement

Purpose : To highlight similarities and differences between two subjects.

Example : "While both novels '1984' and 'Brave New World' delve into dystopian futures, they differ in their portrayal of individual freedom, societal control, and the role of technology."

When you write a thesis statement , it's important to ensure clarity and precision, so the reader immediately understands the central focus of your work.

What is the difference between a thesis and a thesis statement?

While both terms are frequently used interchangeably, they have distinct meanings.

A thesis refers to the entire research document, encompassing all its chapters and sections. In contrast, a thesis statement is a brief assertion that encapsulates the central argument of the research.

Here’s an in-depth differentiation table of a thesis and a thesis statement.

Now, to craft a compelling thesis, it's crucial to adhere to a specific structure. Let’s break down these essential components that make up a thesis structure

15 components of a thesis structure

Navigating a thesis can be daunting. However, understanding its structure can make the process more manageable.

Here are the key components or different sections of a thesis structure:

Your thesis begins with the title page. It's not just a formality but the gateway to your research.

Here, you'll prominently display the necessary information about you (the author) and your institutional details.

Title of your thesis
Your full name
Your department
Your institution and degree program
Your submission date
Your Supervisor's name (in some cases)
Your Department or faculty (in some cases)
Your University's logo (in some cases)
Your Student ID (in some cases)

In a concise manner, you'll have to summarize the critical aspects of your research in typically no more than 200-300 words.

This includes the problem statement, methodology, key findings, and conclusions. For many, the abstract will determine if they delve deeper into your work, so ensure it's clear and compelling.

Acknowledgments

Research is rarely a solitary endeavor. In the acknowledgments section, you have the chance to express gratitude to those who've supported your journey.

This might include advisors, peers, institutions, or even personal sources of inspiration and support. It's a personal touch, reflecting the humanity behind the academic rigor.

A roadmap for your readers, the table of contents lists the chapters, sections, and subsections of your thesis.

By providing page numbers, you allow readers to navigate your work easily, jumping to sections that pique their interest.

List of figures and tables

Research often involves data, and presenting this data visually can enhance understanding. This section provides an organized listing of all figures and tables in your thesis.

It's a visual index, ensuring that readers can quickly locate and reference your graphical data.

Introduction

Here's where you introduce your research topic, articulate the research question or objective, and outline the significance of your study.

Present the research topic : Clearly articulate the central theme or subject of your research.
Background information : Ground your research topic, providing any necessary context or background information your readers might need to understand the significance of your study.
Define the scope : Clearly delineate the boundaries of your research, indicating what will and won't be covered.
Literature review : Introduce any relevant existing research on your topic, situating your work within the broader academic conversation and highlighting where your research fits in.
State the research Question(s) or objective(s) : Clearly articulate the primary questions or objectives your research aims to address.
Outline the study's structure : Give a brief overview of how the subsequent sections of your work will unfold, guiding your readers through the journey ahead.

The introduction should captivate your readers, making them eager to delve deeper into your research journey.

Literature review section

Your study correlates with existing research. Therefore, in the literature review section, you'll engage in a dialogue with existing knowledge, highlighting relevant studies, theories, and findings.

It's here that you identify gaps in the current knowledge, positioning your research as a bridge to new insights.

To streamline this process, consider leveraging AI tools. For example, the SciSpace literature review tool enables you to efficiently explore and delve into research papers, simplifying your literature review journey.

Methodology

In the research methodology section, you’ll detail the tools, techniques, and processes you employed to gather and analyze data. This section will inform the readers about how you approached your research questions and ensures the reproducibility of your study.

Here's a breakdown of what it should encompass:

Research Design : Describe the overall structure and approach of your research. Are you conducting a qualitative study with in-depth interviews? Or is it a quantitative study using statistical analysis? Perhaps it's a mixed-methods approach?
Data Collection : Detail the methods you used to gather data. This could include surveys, experiments, observations, interviews, archival research, etc. Mention where you sourced your data, the duration of data collection, and any tools or instruments used.
Sampling : If applicable, explain how you selected participants or data sources for your study. Discuss the size of your sample and the rationale behind choosing it.
Data Analysis : Describe the techniques and tools you used to process and analyze the data. This could range from statistical tests in quantitative research to thematic analysis in qualitative research.
Validity and Reliability : Address the steps you took to ensure the validity and reliability of your findings to ensure that your results are both accurate and consistent.
Ethical Considerations : Highlight any ethical issues related to your research and the measures you took to address them, including — informed consent, confidentiality, and data storage and protection measures.

Moreover, different research questions necessitate different types of methodologies. For instance:

Experimental methodology : Often used in sciences, this involves a controlled experiment to discern causality.
Qualitative methodology : Employed when exploring patterns or phenomena without numerical data. Methods can include interviews, focus groups, or content analysis.
Quantitative methodology : Concerned with measurable data and often involves statistical analysis. Surveys and structured observations are common tools here.
Mixed methods : As the name implies, this combines both qualitative and quantitative methodologies.

The Methodology section isn’t just about detailing the methods but also justifying why they were chosen. The appropriateness of the methods in addressing your research question can significantly impact the credibility of your findings.

Results (or Findings)

This section presents the outcomes of your research. It's crucial to note that the nature of your results may vary; they could be quantitative, qualitative, or a mix of both.

Quantitative results often present statistical data, showcasing measurable outcomes, and they benefit from tables, graphs, and figures to depict these data points.

Qualitative results , on the other hand, might delve into patterns, themes, or narratives derived from non-numerical data, such as interviews or observations.

Regardless of the nature of your results, clarity is essential. This section is purely about presenting the data without offering interpretations — that comes later in the discussion.

In the discussion section, the raw data transforms into valuable insights.

Start by revisiting your research question and contrast it with the findings. How do your results expand, constrict, or challenge current academic conversations?

Dive into the intricacies of the data, guiding the reader through its implications. Detail potential limitations transparently, signaling your awareness of the research's boundaries. This is where your academic voice should be resonant and confident.

Practical implications (Recommendation) section

Based on the insights derived from your research, this section provides actionable suggestions or proposed solutions.

Whether aimed at industry professionals or the general public, recommendations translate your academic findings into potential real-world actions. They help readers understand the practical implications of your work and how it can be applied to effect change or improvement in a given field.

When crafting recommendations, it's essential to ensure they're feasible and rooted in the evidence provided by your research. They shouldn't merely be aspirational but should offer a clear path forward, grounded in your findings.

The conclusion provides closure to your research narrative.

It's not merely a recap but a synthesis of your main findings and their broader implications. Reconnect with the research questions or hypotheses posited at the beginning, offering clear answers based on your findings.

Reflect on the broader contributions of your study, considering its impact on the academic community and potential real-world applications.

Lastly, the conclusion should leave your readers with a clear understanding of the value and impact of your study.

References (or Bibliography)

Every theory you've expounded upon, every data point you've cited, and every methodological precedent you've followed finds its acknowledgment here.

In references, it's crucial to ensure meticulous consistency in formatting, mirroring the specific guidelines of the chosen citation style .

Proper referencing helps to avoid plagiarism , gives credit to original ideas, and allows readers to explore topics of interest. Moreover, it situates your work within the continuum of academic knowledge.

To properly cite the sources used in the study, you can rely on online citation generator tools to generate accurate citations!

Here’s more on how you can cite your sources.

Often, the depth of research produces a wealth of material that, while crucial, can make the core content of the thesis cumbersome. The appendix is where you mention extra information that supports your research but isn't central to the main text.

Whether it's raw datasets, detailed procedural methodologies, extended case studies, or any other ancillary material, the appendices ensure that these elements are archived for reference without breaking the main narrative's flow.

For thorough researchers and readers keen on meticulous details, the appendices provide a treasure trove of insights.

Glossary (optional)

In academics, specialized terminologies, and jargon are inevitable. However, not every reader is versed in every term.

The glossary, while optional, is a critical tool for accessibility. It's a bridge ensuring that even readers from outside the discipline can access, understand, and appreciate your work.

By defining complex terms and providing context, you're inviting a wider audience to engage with your research, enhancing its reach and impact.

Remember, while these components provide a structured framework, the essence of your thesis lies in the originality of your ideas, the rigor of your research, and the clarity of your presentation.

As you craft each section, keep your readers in mind, ensuring that your passion and dedication shine through every page.

Thesis examples

To further elucidate the concept of a thesis, here are illustrative examples from various fields:

Example 1 (History): Abolition, Africans, and Abstraction: the Influence of the ‘Noble Savage’ on British and French Antislavery Thought, 1787-1807 by Suchait Kahlon.

Example 2 (Climate Dynamics): Influence of external forcings on abrupt millennial-scale climate changes: a statistical modelling study by Takahito Mitsui · Michel Crucifix

Checklist for your thesis evaluation

Evaluating your thesis ensures that your research meets the standards of academia. Here's an elaborate checklist to guide you through this critical process.

Content and structure

Is the thesis statement clear, concise, and debatable?
Does the introduction provide sufficient background and context?
Is the literature review comprehensive, relevant, and well-organized?
Does the methodology section clearly describe and justify the research methods?
Are the results/findings presented clearly and logically?
Does the discussion interpret the results in light of the research question and existing literature?
Is the conclusion summarizing the research and suggesting future directions or implications?

Clarity and coherence

Is the writing clear and free of jargon?
Are ideas and sections logically connected and flowing?
Is there a clear narrative or argument throughout the thesis?

Research quality

Is the research question significant and relevant?
Are the research methods appropriate for the question?
Is the sample size (if applicable) adequate?
Are the data analysis techniques appropriate and correctly applied?
Are potential biases or limitations addressed?

Originality and significance

Does the thesis contribute new knowledge or insights to the field?
Is the research grounded in existing literature while offering fresh perspectives?

Formatting and presentation

Is the thesis formatted according to institutional guidelines?
Are figures, tables, and charts clear, labeled, and referenced in the text?
Is the bibliography or reference list complete and consistently formatted?
Are appendices relevant and appropriately referenced in the main text?

Grammar and language

Is the thesis free of grammatical and spelling errors?
Is the language professional, consistent, and appropriate for an academic audience?
Are quotations and paraphrased material correctly cited?

Feedback and revision

Have you sought feedback from peers, advisors, or experts in the field?
Have you addressed the feedback and made the necessary revisions?

Overall assessment

Does the thesis as a whole feel cohesive and comprehensive?
Would the thesis be understandable and valuable to someone in your field?

Ensure to use this checklist to leave no ground for doubt or missed information in your thesis.

After writing your thesis, the next step is to discuss and defend your findings verbally in front of a knowledgeable panel. You’ve to be well prepared as your professors may grade your presentation abilities.

Preparing your thesis defense

A thesis defense, also known as "defending the thesis," is the culmination of a scholar's research journey. It's the final frontier, where you’ll present their findings and face scrutiny from a panel of experts.

Typically, the defense involves a public presentation where you’ll have to outline your study, followed by a question-and-answer session with a committee of experts. This committee assesses the validity, originality, and significance of the research.

The defense serves as a rite of passage for scholars. It's an opportunity to showcase expertise, address criticisms, and refine arguments. A successful defense not only validates the research but also establishes your authority as a researcher in your field.

Here’s how you can effectively prepare for your thesis defense .

Now, having touched upon the process of defending a thesis, it's worth noting that scholarly work can take various forms, depending on academic and regional practices.

One such form, often paralleled with the thesis, is the 'dissertation.' But what differentiates the two?

Dissertation vs. Thesis

Often used interchangeably in casual discourse, they refer to distinct research projects undertaken at different levels of higher education.

To the uninitiated, understanding their meaning might be elusive. So, let's demystify these terms and delve into their core differences.

Here's a table differentiating between the two.

Wrapping up

From understanding the foundational concept of a thesis to navigating its various components, differentiating it from a dissertation, and recognizing the importance of proper citation — this guide covers it all.

As scholars and readers, understanding these nuances not only aids in academic pursuits but also fosters a deeper appreciation for the relentless quest for knowledge that drives academia.

It’s important to remember that every thesis is a testament to curiosity, dedication, and the indomitable spirit of discovery.

Good luck with your thesis writing!

Frequently Asked Questions

A thesis typically ranges between 40-80 pages, but its length can vary based on the research topic, institution guidelines, and level of study.

A PhD thesis usually spans 200-300 pages, though this can vary based on the discipline, complexity of the research, and institutional requirements.

To identify a thesis topic, consider current trends in your field, gaps in existing literature, personal interests, and discussions with advisors or mentors. Additionally, reviewing related journals and conference proceedings can provide insights into potential areas of exploration.

The conceptual framework is often situated in the literature review or theoretical framework section of a thesis. It helps set the stage by providing the context, defining key concepts, and explaining the relationships between variables.

A thesis statement should be concise, clear, and specific. It should state the main argument or point of your research. Start by pinpointing the central question or issue your research addresses, then condense that into a single statement, ensuring it reflects the essence of your paper.

AI for Meta Analysis — A Comprehensive Guide

Cybersecurity in Higher Education: Safeguarding Students and Faculty Data

How To Write An Argumentative Essay

Developing a Thesis Statement

Many papers you write require developing a thesis statement. In this section you’ll learn what a thesis statement is and how to write one.

Keep in mind that not all papers require thesis statements . If in doubt, please consult your instructor for assistance.

What is a thesis statement?

A thesis statement . . .

Makes an argumentative assertion about a topic; it states the conclusions that you have reached about your topic.
Makes a promise to the reader about the scope, purpose, and direction of your paper.
Is focused and specific enough to be “proven” within the boundaries of your paper.
Is generally located near the end of the introduction ; sometimes, in a long paper, the thesis will be expressed in several sentences or in an entire paragraph.
Identifies the relationships between the pieces of evidence that you are using to support your argument.

Not all papers require thesis statements! Ask your instructor if you’re in doubt whether you need one.

Identify a topic

Your topic is the subject about which you will write. Your assignment may suggest several ways of looking at a topic; or it may name a fairly general concept that you will explore or analyze in your paper.

Consider what your assignment asks you to do

Inform yourself about your topic, focus on one aspect of your topic, ask yourself whether your topic is worthy of your efforts, generate a topic from an assignment.

Below are some possible topics based on sample assignments.

Sample assignment 1

Analyze Spain’s neutrality in World War II.

Identified topic

Franco’s role in the diplomatic relationships between the Allies and the Axis

This topic avoids generalities such as “Spain” and “World War II,” addressing instead on Franco’s role (a specific aspect of “Spain”) and the diplomatic relations between the Allies and Axis (a specific aspect of World War II).

Sample assignment 2

Analyze one of Homer’s epic similes in the Iliad.

The relationship between the portrayal of warfare and the epic simile about Simoisius at 4.547-64.

This topic focuses on a single simile and relates it to a single aspect of the Iliad ( warfare being a major theme in that work).

Developing a Thesis Statement–Additional information

Your assignment may suggest several ways of looking at a topic, or it may name a fairly general concept that you will explore or analyze in your paper. You’ll want to read your assignment carefully, looking for key terms that you can use to focus your topic.

Sample assignment: Analyze Spain’s neutrality in World War II Key terms: analyze, Spain’s neutrality, World War II

After you’ve identified the key words in your topic, the next step is to read about them in several sources, or generate as much information as possible through an analysis of your topic. Obviously, the more material or knowledge you have, the more possibilities will be available for a strong argument. For the sample assignment above, you’ll want to look at books and articles on World War II in general, and Spain’s neutrality in particular.

As you consider your options, you must decide to focus on one aspect of your topic. This means that you cannot include everything you’ve learned about your topic, nor should you go off in several directions. If you end up covering too many different aspects of a topic, your paper will sprawl and be unconvincing in its argument, and it most likely will not fulfull the assignment requirements.

For the sample assignment above, both Spain’s neutrality and World War II are topics far too broad to explore in a paper. You may instead decide to focus on Franco’s role in the diplomatic relationships between the Allies and the Axis , which narrows down what aspects of Spain’s neutrality and World War II you want to discuss, as well as establishes a specific link between those two aspects.

Before you go too far, however, ask yourself whether your topic is worthy of your efforts. Try to avoid topics that already have too much written about them (i.e., “eating disorders and body image among adolescent women”) or that simply are not important (i.e. “why I like ice cream”). These topics may lead to a thesis that is either dry fact or a weird claim that cannot be supported. A good thesis falls somewhere between the two extremes. To arrive at this point, ask yourself what is new, interesting, contestable, or controversial about your topic.

As you work on your thesis, remember to keep the rest of your paper in mind at all times . Sometimes your thesis needs to evolve as you develop new insights, find new evidence, or take a different approach to your topic.

Derive a main point from topic

Once you have a topic, you will have to decide what the main point of your paper will be. This point, the “controlling idea,” becomes the core of your argument (thesis statement) and it is the unifying idea to which you will relate all your sub-theses. You can then turn this “controlling idea” into a purpose statement about what you intend to do in your paper.

Look for patterns in your evidence

Compose a purpose statement.

Consult the examples below for suggestions on how to look for patterns in your evidence and construct a purpose statement.

Franco first tried to negotiate with the Axis
Franco turned to the Allies when he couldn’t get some concessions that he wanted from the Axis

Possible conclusion:

Spain’s neutrality in WWII occurred for an entirely personal reason: Franco’s desire to preserve his own (and Spain’s) power.

Purpose statement

This paper will analyze Franco’s diplomacy during World War II to see how it contributed to Spain’s neutrality.

The simile compares Simoisius to a tree, which is a peaceful, natural image.
The tree in the simile is chopped down to make wheels for a chariot, which is an object used in warfare.

At first, the simile seems to take the reader away from the world of warfare, but we end up back in that world by the end.

This paper will analyze the way the simile about Simoisius at 4.547-64 moves in and out of the world of warfare.

Derive purpose statement from topic

To find out what your “controlling idea” is, you have to examine and evaluate your evidence . As you consider your evidence, you may notice patterns emerging, data repeated in more than one source, or facts that favor one view more than another. These patterns or data may then lead you to some conclusions about your topic and suggest that you can successfully argue for one idea better than another.

For instance, you might find out that Franco first tried to negotiate with the Axis, but when he couldn’t get some concessions that he wanted from them, he turned to the Allies. As you read more about Franco’s decisions, you may conclude that Spain’s neutrality in WWII occurred for an entirely personal reason: his desire to preserve his own (and Spain’s) power. Based on this conclusion, you can then write a trial thesis statement to help you decide what material belongs in your paper.

Sometimes you won’t be able to find a focus or identify your “spin” or specific argument immediately. Like some writers, you might begin with a purpose statement just to get yourself going. A purpose statement is one or more sentences that announce your topic and indicate the structure of the paper but do not state the conclusions you have drawn . Thus, you might begin with something like this:

This paper will look at modern language to see if it reflects male dominance or female oppression.
I plan to analyze anger and derision in offensive language to see if they represent a challenge of society’s authority.

At some point, you can turn a purpose statement into a thesis statement. As you think and write about your topic, you can restrict, clarify, and refine your argument, crafting your thesis statement to reflect your thinking.

As you work on your thesis, remember to keep the rest of your paper in mind at all times. Sometimes your thesis needs to evolve as you develop new insights, find new evidence, or take a different approach to your topic.

Compose a draft thesis statement

If you are writing a paper that will have an argumentative thesis and are having trouble getting started, the techniques in the table below may help you develop a temporary or “working” thesis statement.

Begin with a purpose statement that you will later turn into a thesis statement.

Assignment: Discuss the history of the Reform Party and explain its influence on the 1990 presidential and Congressional election.

Purpose Statement: This paper briefly sketches the history of the grassroots, conservative, Perot-led Reform Party and analyzes how it influenced the economic and social ideologies of the two mainstream parties.

Question-to-Assertion

If your assignment asks a specific question(s), turn the question(s) into an assertion and give reasons why it is true or reasons for your opinion.

Assignment : What do Aylmer and Rappaccini have to be proud of? Why aren’t they satisfied with these things? How does pride, as demonstrated in “The Birthmark” and “Rappaccini’s Daughter,” lead to unexpected problems?

Beginning thesis statement: Alymer and Rappaccinni are proud of their great knowledge; however, they are also very greedy and are driven to use their knowledge to alter some aspect of nature as a test of their ability. Evil results when they try to “play God.”

Write a sentence that summarizes the main idea of the essay you plan to write.

Main idea: The reason some toys succeed in the market is that they appeal to the consumers’ sense of the ridiculous and their basic desire to laugh at themselves.

Make a list of the ideas that you want to include; consider the ideas and try to group them.

nature = peaceful
war matériel = violent (competes with 1?)
need for time and space to mourn the dead
war is inescapable (competes with 3?)

Use a formula to arrive at a working thesis statement (you will revise this later).

although most readers of _______ have argued that _______, closer examination shows that _______.
_______ uses _______ and _____ to prove that ________.
phenomenon x is a result of the combination of __________, __________, and _________.

What to keep in mind as you draft an initial thesis statement

Beginning statements obtained through the methods illustrated above can serve as a framework for planning or drafting your paper, but remember they’re not yet the specific, argumentative thesis you want for the final version of your paper. In fact, in its first stages, a thesis statement usually is ill-formed or rough and serves only as a planning tool.

As you write, you may discover evidence that does not fit your temporary or “working” thesis. Or you may reach deeper insights about your topic as you do more research, and you will find that your thesis statement has to be more complicated to match the evidence that you want to use.

You must be willing to reject or omit some evidence in order to keep your paper cohesive and your reader focused. Or you may have to revise your thesis to match the evidence and insights that you want to discuss. Read your draft carefully, noting the conclusions you have drawn and the major ideas which support or prove those conclusions. These will be the elements of your final thesis statement.

Sometimes you will not be able to identify these elements in your early drafts, but as you consider how your argument is developing and how your evidence supports your main idea, ask yourself, “ What is the main point that I want to prove/discuss? ” and “ How will I convince the reader that this is true? ” When you can answer these questions, then you can begin to refine the thesis statement.

Refine and polish the thesis statement

To get to your final thesis, you’ll need to refine your draft thesis so that it’s specific and arguable.

Ask if your draft thesis addresses the assignment
Question each part of your draft thesis
Clarify vague phrases and assertions
Investigate alternatives to your draft thesis

Consult the example below for suggestions on how to refine your draft thesis statement.

Sample Assignment

Choose an activity and define it as a symbol of American culture. Your essay should cause the reader to think critically about the society which produces and enjoys that activity.

Ask The phenomenon of drive-in facilities is an interesting symbol of american culture, and these facilities demonstrate significant characteristics of our society.This statement does not fulfill the assignment because it does not require the reader to think critically about society.

Drive-ins are an interesting symbol of American culture because they represent Americans’ significant creativity and business ingenuity.

Among the types of drive-in facilities familiar during the twentieth century, drive-in movie theaters best represent American creativity, not merely because they were the forerunner of later drive-ins and drive-throughs, but because of their impact on our culture: they changed our relationship to the automobile, changed the way people experienced movies, and changed movie-going into a family activity.

While drive-in facilities such as those at fast-food establishments, banks, pharmacies, and dry cleaners symbolize America’s economic ingenuity, they also have affected our personal standards.

While drive-in facilities such as those at fast- food restaurants, banks, pharmacies, and dry cleaners symbolize (1) Americans’ business ingenuity, they also have contributed (2) to an increasing homogenization of our culture, (3) a willingness to depersonalize relationships with others, and (4) a tendency to sacrifice quality for convenience.

This statement is now specific and fulfills all parts of the assignment. This version, like any good thesis, is not self-evident; its points, 1-4, will have to be proven with evidence in the body of the paper. The numbers in this statement indicate the order in which the points will be presented. Depending on the length of the paper, there could be one paragraph for each numbered item or there could be blocks of paragraph for even pages for each one.

Complete the final thesis statement

The bottom line.

As you move through the process of crafting a thesis, you’ll need to remember four things:

Context matters! Think about your course materials and lectures. Try to relate your thesis to the ideas your instructor is discussing.
As you go through the process described in this section, always keep your assignment in mind . You will be more successful when your thesis (and paper) responds to the assignment than if it argues a semi-related idea.
Your thesis statement should be precise, focused, and contestable ; it should predict the sub-theses or blocks of information that you will use to prove your argument.
Make sure that you keep the rest of your paper in mind at all times. Change your thesis as your paper evolves, because you do not want your thesis to promise more than your paper actually delivers.

In the beginning, the thesis statement was a tool to help you sharpen your focus, limit material and establish the paper’s purpose. When your paper is finished, however, the thesis statement becomes a tool for your reader. It tells the reader what you have learned about your topic and what evidence led you to your conclusion. It keeps the reader on track–well able to understand and appreciate your argument.

Writing Process and Structure

This is an accordion element with a series of buttons that open and close related content panels.

Getting Started with Your Paper

Interpreting Writing Assignments from Your Courses

Generating Ideas for

Creating an Argument

Thesis vs. Purpose Statements

Architecture of Arguments

Working with Sources

Quoting and Paraphrasing Sources

Using Literary Quotations

Citing Sources in Your Paper

Drafting Your Paper

Generating Ideas for Your Paper

Introductions

Paragraphing

Developing Strategic Transitions

Conclusions

Revising Your Paper

Peer Reviews

Reverse Outlines

Revising an Argumentative Paper

Revision Strategies for Longer Projects

Finishing Your Paper

Twelve Common Errors: An Editing Checklist

How to Proofread your Paper

Writing Collaboratively

Collaborative and Group Writing

Research Essentials

Develop a Question
Identify Keywords
Search Tips
Too Few/Many Results?
Use Sources
Scholarly vs Popular

What Is a Thesis?

Crafting a thesis.

Cite Sources
Find Articles
Primary Sources

More Resources

How to Write a Thesis Statement IU Writing Tutorial Services
Tips and Examples for Writing Thesis Statements Purdue OWL

A thesis is the main point or argument of an information source. (Many, but not all, writing assignments, require a thesis.) Thesis are often answer your research question. Note that it does not have to be the only answer to your research question, a strong thesis question gives a reasonable answer. Below are some characteristics of a strong thesis.

A strong thesis is:

Arguable: Can be supported by evidence and analysis, and can be disagreed with.
Unique: Says something new and interesting.
Concise and clear: Explained as simply as possible, but not at the expense of clarity.
Unified: All parts are clearly connected.
Focused and specific: Can be adequately and convincingly argued within the the paper, scope is not overly broad.
Significant: Has importance to readers, answers the question "so what?"

Reading previous research is vital to developing a strong thesis. By reading what others have to say about, you'll learn what interests you, and develop interesting questions with interesting answers. Exploring broadly can help you refine your central point.

Conduct Background Research

A strong thesis is specific and unique, so you first need knowledge of the general research topic. Background research will help you narrow your research focus by answering the obvious questions with established answers; it will also help contextualize your argument in relation to other research.

Narrow the Research Topic

Ask questions as you review sources:

What aspect(s) of the topic interest you most?
Are there disagreements between different papers and authors?
What questions or concerns does the topic raise for you? Example of a general research topic: Climate change and carbon emissions Example of more narrow topic: U.S. government policies on carbon emissions

Formulate and explore a relevant research question

Before committing yourself to a single viewpoint, formulate a specific question to explore. Consider different perspectives on the issue, and find sources that represent these varying views. Reflect on strengths and weaknesses in the sources' arguments. Consider sources that challenge these viewpoints.

Example: What role does and should the U.S. government play in regulating carbon emissions?

Develop a working thesis

A working thesis has a clear focus but is not yet be fully formed. It is a good foundation for further developing a more refined argument. Example: The U.S. government has the responsibility to help reduce carbon emissions through public policy and regulation. This thesis has a clear focus but leaves some major questions unanswered. For example, why is regulation of carbon emissions important? Why should the government be held accountable for such regulation?

Continue research on the more focused topic

Is the topic:

broad enough to yield sufficient sources and supporting evidence?
narrow enough for in-depth and focused research?
original enough to offer a new and meaningful perspective that will interest readers?

Fine-tune the thesis

Your thesis will probably evolve as you gather sources and ideas. If your research focus changes, you may need to re-evaluate your search strategy and to conduct additional research. This is usually a good sign of the careful thought you are putting into your work!

Example: Because climate change, which is exacerbated by high carbon emissions, adversely affects almost all citizens, the U.S. government has the responsibility to help reduce carbon emissions through public policy and regulation.

<< Previous: Scholarly vs Popular
Next: Cite Sources >>
Last Updated: Nov 13, 2023 10:40 AM
URL: https://guides.libraries.indiana.edu/essentials

Social media

Instagram for Herman B Wells Library
Facebook for IU Libraries

Additional resources

Featured databases.

Resource available to authorized IU Bloomington users (on or off campus) OneSearch@IU
Resource available to authorized IU Bloomington users (on or off campus) Academic Search (EBSCO)
Resource available to authorized IU Bloomington users (on or off campus) ERIC (EBSCO)
Resource available to authorized IU Bloomington users (on or off campus) Nexis Uni
Resource available without restriction HathiTrust Digital Library
Databases A-Z
Resource available to authorized IU Bloomington users (on or off campus) Google Scholar
Resource available to authorized IU Bloomington users (on or off campus) JSTOR
Resource available to authorized IU Bloomington users (on or off campus) Web of Science
Resource available to authorized IU Bloomington users (on or off campus) Scopus
Resource available to authorized IU Bloomington users (on or off campus) WorldCat

IU Libraries

Diversity Resources
About IU Libraries
Alumni & Friends
Departments & Staff
Jobs & Libraries HR
Intranet (Staff)
IUL site admin

Jump to navigation

Undergraduate Admissions
Transfer Admissions
Graduate Admissions
Honors and Scholars Admissions
International Admissions
Law Admissions
Office of Financial Aid
Orientation
Pre-College Programs
Scholarships
Tuition & Fees
Academic Calendar
Academic Colleges
Degree Programs
Online Programs
Class Schedule
Workforce Development
Sponsored Programs and Research Services
Technology Transfer
Faculty Expertise Database
Research Centers
College of Graduate Studies
Institutional Research and Analysis
At a Glance
Concerned Vikes
Free Speech on Campus
Policies and Procedures
Messages & Updates
In the News
Board of Trustees
Senior Leadership Team
Services Near CSU

Cleveland State University

Search this site

Thesis statement.

Definition:

The thesis is usually considered the most important sentence of your essay because it outlines the central purpose of your essay in one place. A good thesis will link the subject of an essay with a controlling idea. Consider, for example, the following thesis:

People in the past spent a great deal of effort protecting themselves from witches. Subject: people feared witches Controlling Idea: people spent a great deal of effort protecting themselves

In a short essay, a thesis statement appears at, or near, the end of the introductory paragraph of the paper so that readers know the topic of the essay before they see the writer's statement of the central purpose of the essay. This way the first paragraph helps the reader understand why the writer is writing.

A thesis should be narrow in focus in order to allow the fullest exploration of its issues as possible, and it should reflect the type of paper that follows, whether it be persuasive or informative. Narrowing the focus of the thesis may require posing questions about it to yourself before committing to a final version.

What follows is a method for writing thesis statements that many writers have found useful (we found it in Chapter 3 of The Allyn & Bacon Handbook ).

1. Decide what you are writing about:

A clear, concise thesis statement does more than outline the subject in question; it makes the reader aware of the writer's stand on the subject in question, connecting a subject with a controlling idea.

2. Think about all the elements your paper will deal with:

A thesis generally consists of a subject that contains within itself a number of smaller facts; the topic sentence of each paragraph that makes up the body of the paper should refer (in some clear way) back to the ideas contained within the thesis statement in order to keep the paper from digressing.

3. Think about the purpose and tone of your paper:

A thesis statement should contain the main point of the paper and suggest to the reader a direction that the paper will take in exploring, proving, or disproving that main point.

4. State your main point in a sentence or two:

A good writer can assert the main idea of a short, coherent essay briefly. Instead of rambling, be as straightforward as possible.

5. Revise your thesis as you develop your paper:

A final version of a thesis statement will only be available after a draft of the paper it is a part of has been completed. The focus of the paper may change and evolve over the period it is written in; necessarily, the thesis statement should be revised to reflect the alterations in the paper.

Few writers finish a paper writing about the exact topic they begin with. While you write a paper, your main point may change. As you're finishing, make sure your thesis statement has changed along with the subject and controlling ideas of your paper.

Questions, comments, and other sundry things may be sent to [email protected]

[Top of Page]

school Campus Bookshelves
menu_book Bookshelves
perm_media Learning Objects
login Login
how_to_reg Request Instructor Account
hub Instructor Commons
Download Page (PDF)
Download Full Book (PDF)
Periodic Table
Physics Constants
Scientific Calculator
Reference & Cite
Tools expand_more
Readability

selected template will load here

This action is not available.

4.3: What is a Thesis Statement?

Last updated
Save as PDF
Page ID 12059
Kathy Boylan

Once the topic has been narrowed to a workable subject, then determine what you are going to say about it; you need to come up with your controlling or main idea. A thesis is the main idea of an essay. It communicates the essay’s purpose with clear and concise wording and indicates the direction and scope of the essay. It should not just be a statement of fact nor should it be an announcement of your intentions. It should be an idea, an opinion of yours that needs to be explored, expanded, and developed into an argument .

A thesis statement:

tells the reader how you will interpret the significance of the subject matter under discussion.
is a road map for the paper; in other words, it tells the reader what to expect from the rest of the paper.
is an interpretation of a question or subject, not the subject itself. The subject, or topic, of an essay might be World War II or Moby Dick ; a thesis must then offer a way to understand the war or the novel.
makes a claim that others might dispute.
is usually a single sentence somewhere in the introductory paragraph that presents the writer’s argument to the reader. However, as essays get longer, a sentence alone is usually not enough to contain a complex thesis. The rest of the paper, the body of the essay, gathers and organizes evidence that will persuade the readers of the logic of their interpretation.

If an assignment asks you to take a position or develop a claim about a subject, you may need to convey that position or claim in a thesis statement near the beginning of your draft. The assignment may not explicitly state that the writer needs a thesis statement because the instructor may assume the writer will include one. When an assignment asks you to analyze, to interpret, to compare and contrast, to demonstrate cause and effect, or to take a stand on an issue, it is likely that you are being asked to develop a thesis and to support it persuasively.

How do I get a thesis?

A thesis is the result of a lengthy thinking process. Formulating a thesis is not the first thing you do after reading an essay assignment. Before you develop an argument on any topic, you have to collect and organize evidence, look for possible relationships between known facts (such as surprising contrasts or similarities), and think about the significance of these relationships. (See chapter on argument for more detailed information on building an argument.) Once you have done this thinking, you will probably have a “working thesis,” a basic or main idea, an argument that you can support with evidence. It is deemed a “working thesis” because it is a work in progress, and it is subject to change as you move through the writing process. Writers use all kinds of techniques to stimulate their thinking and to help them clarify relationships or comprehend the broader significance of a topic to arrive at a thesis statement.

For example, there is the question strategy. One way to start identifying and narrowing a thesis idea is to form a question that you want to answer. For example, if the starting question was “Do cats have a positive effect on people with depression? If so, what are three effects? The question sends you off to explore for answers. You then begin developing support. The first answer you might find is that petting cats lowers blood pressure, and, further question how that works. From your findings (research, interviews, background reading, etc.), you might detail how that happens physically or you might describe historical evidence. You could explain medical research that illustrates the concept. Then you have your first supporting point — as well as the first prong of your thesis: Cats have a positive effect on people with depression because they can lower blood pressure.... When you start with a specific question and find the answers, the argument falls into place. The answer to the question becomes the thesis, and how the answer was conceived becomes the supporting points (and, usually, the topic sentences for each point).

How do I know if my thesis is strong?

If there is time, run it by the instructor or make an appointment at the Writing Center ( https://tinyurl.com/ybqafrbf ) to get some feedback. Even if you do not have time to get advice elsewhere, you can do some thesis evaluation of your own.

When reviewing the first draft and its working thesis, ask the following:

TOPIC + CLAIM = THESIS STATEMENT

Animals + Dogs make better pets than cats. =When it comes to animals, dogs make better pets than cats because they are more trainable, more social, and more empathetic.
Movies & Emotions + Titanic evoked many emotions. = The movie Titanic evoked many emotions from an audience.
Arthur Miller & Death of a Salesman + Miller’s family inspired the Loman family. = Arthur Miller’s family and their experiences during the Great Depression inspired the creation of the Loman family in his play Death of a Salesman .

( https://tinyurl.com/y8sfjale ).

Exercise: Creating Effective Thesis Statements

Using the formula, create effective thesis statements for the following topics:

Drone Technology
Helicopter Parents

Then have a partner check your thesis statements to see if they pass the tests to be strong thesis statements.

Once a working thesis statement has been created, then it is time to begin building the body of the essay. Get all of the key supporting ideas written down, and then you can begin to flesh out the body paragraphs by reading, asking, observing, researching, connecting personal experiences, etc. Use the information from below to maintain the internal integrity of the paragraphs and smooth the flow of your ideas.

Have a language expert improve your writing

Run a free plagiarism check in 10 minutes, automatically generate references for free.

Knowledge Base
Dissertation
What Is a Thesis? | Ultimate Guide & Examples

What Is a Thesis? | Ultimate Guide & Examples

Published on 15 September 2022 by Tegan George . Revised on 5 December 2023.

A thesis is a type of research paper based on your original research. It is usually submitted as the final step of a PhD program in the UK.

Writing a thesis can be a daunting experience. Indeed, alongside a dissertation , it is the longest piece of writing students typically complete. It relies on your ability to conduct research from start to finish: designing your research , collecting data , developing a robust analysis, drawing strong conclusions , and writing concisely .

Thesis template

Download Word template Download Google Docs template

Instantly correct all language mistakes in your text

Be assured that you'll submit flawless writing. Upload your document to correct all your mistakes.

You may have heard the word thesis as a standalone term or as a component of academic writing called a thesis statement . Keep in mind that these are two very different things.

A thesis statement is a very common component of an essay, particularly in the humanities. It usually comprises 1 or 2 sentences in the introduction of your essay , and should clearly and concisely summarise the central points of your academic essay .
A thesis is a long-form piece of academic writing, often taking more than a full semester to complete. It is generally a degree requirement to complete a PhD program.
In many countries, particularly the UK, a dissertation is generally written at the bachelor’s or master’s level.
In the US, a dissertation is generally written as a final step toward obtaining a PhD.

Prevent plagiarism, run a free check.

The final structure of your thesis depends on a variety of components, such as:

Your discipline
Your theoretical approach

Humanities theses are often structured more like a longer-form essay . Just like in an essay, you build an argument to support a central thesis.

Thesis examples

We’ve compiled a short list of thesis examples to help you get started.

Example thesis #1: ‘Abolition, Africans, and Abstraction: the Influence of the “Noble Savage” on British and French Antislavery Thought, 1787-1807’ by Suchait Kahlon.
Example thesis #2: ‘”A Starving Man Helping Another Starving Man”: UNRRA, India, and the Genesis of Global Relief, 1943-1947’ by Julian Saint Reiman.

The very first page of your thesis contains all necessary identifying information, including:

Your full title
Your full name
Your department
Your institution and degree program
Your submission date.

Sometimes the title page also includes your student ID, the name of your supervisor, or the university’s logo. Check out your university’s guidelines if you’re not sure.

The only proofreading tool specialized in correcting academic writing

The academic proofreading tool has been trained on 1000s of academic texts and by native English editors. Making it the most accurate and reliable proofreading tool for students.

Correct my document today

Theoretical framework

Your literature review can often form the basis for your theoretical framework, but these are not the same thing. A theoretical framework defines and analyses the concepts and theories that your research hinges on.

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the ‘Cite this Scribbr article’ button to automatically add the citation to our free Reference Generator.

George, T. (2023, December 05). What Is a Thesis? | Ultimate Guide & Examples. Scribbr. Retrieved 2 April 2024, from https://www.scribbr.co.uk/thesis-dissertation/thesis-ultimate-guide/

Is this article helpful?

Tegan George

Other students also liked, dissertation & thesis outline | example & free templates, how to write a thesis or dissertation conclusion, how to write a thesis or dissertation introduction.

Davidson Writer

Academic Writing Resources for Students

Main navigation

Evolving a central claim: example 1, how an initial idea evolves to become a central claim.

In their Writing Analytically textbook, Writing Studies scholars David Rosenwsasser and Jill Stephens illustrate how a central claim evolves by revealing a set of questions a student writer asks of her object of study. Here is their illustration of that process:

Because the writing process is a way not just of recording but of discovering ideas, writers, especially in the early stages of drafting, often set out with one idea or direction in mind and then, in the process of writing, happen upon another, potentially better idea that only begins to emerge in the draft. Once you’re recognized them, these emerging thoughts may lead to your evolving a markedly different central claim, or they may provide you with the means of extending your paper’s original thesis well beyond the point you settled for initially.

Writers undertake this kind of conceptual revision–locating and defining the central claim–in different ways. Some writers rely on repeatedly revising while they work their way through a first draft (which, when finished, will b e close to a final draft). Others move through the first draft without much revision and then comprehensively rethink and restructure it (sometimes two, three, or more times).Whatever mode of revision works best for you, the thinking processes we demonstrate here are central. They are the common denominators of he various stages of the drafting process.

Our means of demonstrating how writers use exploratory writing to locate and develop a workable thesis [central claim] is to take you through the steps a student writer would follow in revising her initial draft on a painting, Las Meninas (Spanish for “the ladies in waiting”) by the seventeenth-century painter, Diego Velázquez. We are using a paper on a painting because all of the writer’s data (the details of the painting) are on one page, allowing you to think with the writer as she develops her ideas.

As you read the draft, watch how the writer goes about developing the claim made at the end of her first paragraph–that, despite its complexity, the painting clearly reveals at least some of the painter’s intentions (referred to elsewhere in the paper as what the painting is saying, what it suggests, or what the painter wants). We have underlined each appearance of potential central claims in the text of the paper. Using square brackets at the ends of paragraphs, we have described the writer’s methods for arriving at ideas: NOTICE AND FOCUS, THE METHOD, and ASKING “SO WHAT?”

There are a number of good things about this student paper when considered as an exploratory draft. Studying it will help you train yourself to turn a more discriminating eye on your own works in progress, especially in that all-important early stage in which you are writing in order to discover ideas.

A Student’s Work in Progress

Draft Title: Velázquez’s Intentions in Las Meninas

Paragraph 1

Velázquez has been noted as being one of the best Spanish artists of all time. It seems that as Velázquez got older, his paintings became better. Toward the end of his life, he painted his masterpiece, Las Meninas. Out of all his works, Las Meninas is the only known self-portrait of Velázquez. There is much to be said about Las Meninas. The painting is very complex, but some of the intentions that Velázquez had in painting Las Meninas are very clear. [The writer opens with background information and a broad working central claim (underlined).] Paragraph 2 First, we must look at the painting as a whole. The question that must be answered is who is in the painting? The people are all members of the Royal Court of the Spanish monarch Philip IV. In the center is the king’s daughter, who eventually became Empress of Spain. Around her are her meninas or ladies-in-waiting. These meninas are all daughters of influential men. To the right of the meninas is a dwarf who is a servant, and the family dog who looks fierce but is easily tamed by the foot of a child. The more unique people in the painting are Velázquez, himself, who stands to the left in front of the canvas; the king and queen, whose faces are captured in the obscure mirror; the man in the doorway; and the nun and man behind the meninas . To analyze this painting further, the relationship between characters must be understood. [The writer describes the evidence and arrives at an operating assertion—focusing on the relationship among characters.]

Paragraph 3

Where is this scene occurring? Most likely it is in the palace. But why is there no visible furniture? Is it because Velázquez didn’t want the viewer to become distracted from his true intentions? I believe it is to show that this is not just a painting of an actual event. This is an event out of his imagination. [The writer begins pushing observations to tentative conclusions by ASKING SO WHAT?] Paragraph 4 Now, let us become better acquainted with the characters. The child in the center is the most visible. All the light is shining on her. Maybe Velázquez is suggesting that she is the next light for Spain and that even God has approved her by shining all the available light on her. Back in those days there was a belief in the divine right of kings, so this just might be what Velázquez is saying. [The writer starts ranking evidence for importance and continues to ask, SO WHAT?; she arrives at a possible interpretation of the painter’s intention.]

Paragraph 5

The next people of interest are the ones behind the meninas . The woman in the habit might be a nun and the man a priest. The king and queen are in the mirror, which is to suggest they are present, but they are not as visible as they might be. Velázquez suggests that they are not always at the center where everyone would expect them to be. [The writer continues using NOTICE AND FOCUS plus asking SO WHAT?; in addition to looking for pattern in the painting’s details, the writer has begun to notice evidence—the minimal presence of the king and queen in the painting—that could complicated her initial interpretation about the divine right of kings.]

Paragraph 6

The last person and the most interesting is Velázquez. He dominates the painting along with the little girl. He takes up the whole left side along with his gigantic easel. But what is he painting? As I previously said, he might be painting the king and queen. But I also think he could be pretending to paint us, the viewers. The easel really gives this portrait an air of mystery because Velázquez knows that we, the viewers, want to know what he is painting. [The writer locates what she finds to be the most significant detail—the size and prominence of the painter.]

Paragraph 7

The appearance of Velázquez is also interesting. His eyes are focused outward here. They are not focused on what is going on around him. It is a steady stare. Also interesting is his confident stance. He was confident enough to place himself in the painting of the royal court. I think that Velázquez wants the king to give him the recognition he deserves by including him in the “family.” And the symbol of his vest is the symbol given to a painter by the king to show that his status and brilliance have been appreciated by the monarch. It is unknown how it got there. It is unlikely that Velázquez put it there himself. That would be too outright, and Velázquez was the type to give his messages subtly. Some say that after Velázquez’s death, King Philip IV himself painted it to finally give Velázquez the credit he deserved for being a loyal friend and servant. [The writer continues to analyze the most significant detail and to ask SO WHAT? about the painter’s appearance; this takes her to three tentative central claims (underlined above).]

Paragraph 8

I believe that Velázquez was very ingenious by putting his thoughts and feelings into a painting. He didn’t want to offend the kind, who had done so much for him. It paid off for Velázquez because he did finally get what he wanted, even if it was after he died. [The writer concludes and is now ready to redraft to tighten links between evidence and claims, formulate a better central claim, and make this central claim evolve.]

From Details to Ideas: Arriving at a WorkingThesis in an Exploratory Draft

An exploratory draft uses writing as a means of arriving at a working central claim that the next draft can more fully evolve. Most writers find that their best ideas emerge near the end of the exploratory draft, which is the case in this student’s draft (see the three claims underlined in Paragraph 7).

The Las Meninas paper is a good exploratory draft. The writer has begun to interpret details and draw possible conclusions from what she sees, rather than just describing the scene depicted on the canvas or responding loosely to it with her unanalyzed impressions. The move from description to analysis and interpretation begins when you select certain details in your evidence as more important than others and explain what they seem to you to suggest. The writer has done both of these things, and so has gotten to the point where she can begin methodically evolving her initial ideas into a perceptive analysis.

What is especially good about the draft is that it reveals the writer’s willingness to push on from her first idea (reading the painting as an endorsement of the divine right of kings, expressed by the light shining on the princess) by seeking out complicating evidence. The process of revising for ideas begins in earnest when you start checking to make sue that the thesis you have formulated accounts for as much of the available evidence as possible and does not avoid evidence that might complicate or contradict it.

The writer’s first idea (about divine right), for example, does not account for enough of the evidence and is undermined by evidence that clearly doesn’t fit, such as the small size and decentering of the king and queen, and the large size and foregrounding of the painter himself. Rather than ignoring these troublesome details, the writer instead zooms in on them. She focuses on the painter’s representation of himself and of his employers, the king and queen, as the most significant evidence to be taken into account and analyzed in depth.

Finish Your Essay Today! EssayBot Suggests Best Contents and Helps You Write. No Plagiarism!

Is essay writing service legal.

Essay writing services are legal if the company has passed a number of necessary checks and is licensed. This area is well developed and regularly monitored by serious services. If a private person offers you his help for a monetary reward, then we would recommend you to refuse his offer. A reliable essay writing service will always include terms of service on their website. The terms of use describe the clauses that customers must agree to before using a product or service. The best online essay services have large groups of authors with diverse backgrounds. They can complete any type of homework or coursework, regardless of field of study, complexity, and urgency.

When you contact the company Essayswriting, the support service immediately explains the terms of cooperation to you. You can control the work of writers at all levels, so you don't have to worry about the result. To be sure of the correctness of the choice, the site contains reviews from those people who have already used the services.

Finished Papers

Customer Reviews

Get access to the final draft

You will be notified once the essay is done. You will be sent a mail on your registered mail id about the details of the final draft and how to get it.

Synthesis and clinical application of new drugs approved by FDA in 2022

Open access
Published: 04 September 2023
Volume 4 , article number 26 , ( 2023 )

Cite this article

You have full access to this open access article

Jing-Yi Zhang 1 ,
Ya-Tao Wang 2 , 3 ,
Lu Sun 3 , 4 ,
Sai-Qi Wang 3 &
Zhe-Sheng Chen 5

2702 Accesses

1 Altmetric

Explore all metrics

The pharmaceutical industry had a glorious year in 2022, with a total of 37 new drugs including 20 new chemical entities (NCEs) and 17 new biological entities (NBEs) approved by the Food and Drug Administration (FDA). These drugs are mainly concentrated in oncology, central nervous system, antiinfection, hematology, cardiomyopathy, dermatology, digestive system, ophthalmology, MRI enhancer and other therapeutic fields. Of the 37 drugs, 25 (68%) were approved through an expedited review pathway, and 19 (51%) were approved to treat rare diseases. These newly listed drugs have unique structures and new mechanisms of action, which can serve as lead compounds for designing new drugs with similar biological targets and enhancing therapeutic efficacy. This review aims to outline the clinical applications and synthetic methods of 19 NCEs newly approved by the FDA in 2022, but excludes contrast agent (Xenon Xe-129). We believe that an in-depth understanding of the synthetic methods of drug molecules will provide innovative and practical inspiration for the development of new, more effective, and practical synthetic techniques. According to the therapeutic areas of these 2022 FDA-approved drugs, we have classified these 19 NCEs into seven categories and will introduce them in the order of their approval for marketing.

Nanoparticles for Cancer Therapy: Current Progress and Challenges

Shreelaxmi Gavas, Sameer Quazi & Tomasz M. Karpiński

An Overview of Drug Delivery Systems

Deep Insight of Design, Mechanism, and Cancer Theranostic Strategy of Nanozymes

Lu Yang, Shuming Dong, … Piaoping Yang

Avoid common mistakes on your manuscript.

Introduction

The pharmaceutical industry is constantly evolving, with new drugs being developed and approved by the FDA every year. These new drugs offer hope for patients suffering from various diseases and conditions, and they represent a significant advancement in medical science. In 2022, the FDA approved 37 new drugs that have the potential to revolutionize the treatment of various diseases. Of the 37 new drugs, 20 (54%) new drugs belong to new chemical entity (NCE), and 17 (46%) new drugs belong to new biological entity (NBE) [ 1 ]. As shown in Table S 1 , we summarized the drug names, research & development companies, active ingredients, approval dates, indications, and other information of the 37 new drugs [ 2 ]. By analyzing the approved drugs and their indications [ 3 ], it can be found that the main therapeutic field is still oncology, and 10 new oncologic drugs were approved (accounting for 27% of all approved drugs). Seven drugs were approved in the field of the central nervous system (accounting for 19% of the total), five drugs were approved in the field of dermatology (14%), four drugs were approved in the field of anti-infective (accounting for 11% of the total), and three drugs were approved in the fields of hematology (accounting for 8% of the total). Two drugs (5%) were approved in ophthalmology and metabolism respectively, and one drug (3% of the total) was approved in the digestive system and cardiomyopathy respectively. Of these 37 new drugs, up to 25 (68%), new drugs were reviewed and approved through the FDA Center for Drug Evaluation and Research (CDER) accelerated approval process. These accelerated approvals are divided into the following categories: fast track, accelerated approval, priority review, and breakthrough therapy. Among them, 18 new drugs received priority review, 9 new drugs obtained fast track, 4 new Drugs received accelerated approval and 13 new drugs obtained breakthrough therapy, including 6 NCEs and 7 NBEs. It is worth noting that 19 (51%) new drugs were approved to treat rare diseases: For example, Enjaymo is used for the treatment of cold agglutinin disease (CAD), a rare, chronic, serious, autoimmune hemolytic anemia disease [ 4 , 5 ]; Myelofibrosis (MF) is an uncommon condition characterized by abnormalities in the production of blood cells and the presence of fibrosis in the bone marrow [ 6 ], and Vonjo received approval to treat primary and secondary MF in adult patients who have experienced a substantial decrease in their platelet levels [ 7 ]; Amvuttra was approved by FDA to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTR), a genetic condition resulting from mutations in the TTR gene [ 8 , 9 ]. Compared with the 50 drugs approved by the FDA in 2021 (36 NCEs and 14 NBEs), although the number of drugs approved in 2022 is relatively small, there are still some remarkable achievements. For example, Tirzepatide is the first-in-class glucose-lowering drug approved in recent years with a new mechanism of action. In addition to type 2 diabetes, it has shown good potential for treating obesity. The HIV-1 capsid inhibitor lenacapavir can be taken once every six months. Deucravacitinib, a tyrosine kinase 2 inhibitor used to treat psoriasis, the dual-specificity antibody faricimab-svoa for the treatment of macular degeneration, and the antibody–drug conjugate mirvetuximab soravtansine-gynx targeting folate receptor alpha to treat platinum-resistant ovarian cancer have shown good market value.

As far as we know, the study of the synthetic methods of new chemical molecules and their mechanisms of action in clinical applications will greatly promote the development of new drugs, and the summary of newly introduced drugs will provide innovative and practical inspiration for new drug discovery [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Therefore, the purpose of this review is to provide an overview of 19 NCEs approved by the FDA in 2022 (Fig. 1 ), with a focus on the synthesis of these drugs, their mechanism of action, and their potential benefits and risks. The logical sequence of this review will be to first provide an overview of the new drugs approved by the FDA in 2022 (Table S 1 ), followed by a detailed analysis of the 19 NCEs. Finally, the review will conclude with a summary of the key findings and their implications for healthcare professionals. The review will be of great value to physicians, pharmacists, and other healthcare professionals who are involved in the treatment of patients with the diseases and conditions targeted by these drugs.

Chemical structures of FDA-approved drugs in 2022

Anti-infective drugs

Oteseconazole (vivjoa).

Oteseconazole, developed by Mycovia, was given priority review and approved by the FDA on April 26, 2022, which was sold under the brand name Vivjoa, to prevent recurrent vulvovaginal candidiasis (RVVC) in women with no reproductive potential [ 21 , 22 ]. As an orally active anti-fungal agent, oteseconazole is a highly potent and selective inhibitor of Candida albicans CYP51 with a Ki value of below 39 nM, showing no significant effect on human CYP51 [ 23 , 24 , 25 ]. Thanks to the tetrazole moiety, oteseconazole features high selectivity for fungal CYP51 over human P450s, effectively decreasing off-target interactions, which is obviously distinct from previously discovered azole antifungals [ 26 ]. Compared with oteseconazole, triazole or imidazole-containing fluconazole or ketoconazole causes significant drug-drug interactions due to their effect on human CYPs [ 27 , 28 , 29 ]. By targeting CYP5, oteseconazole blocks the transformation of lanosterol to ergosterol, a sterol necessary for the formation and maintenance of fungal cell membrane integrity, thus exerting antifungal activity toward RVVC-related microorganisms, including Candida dubliniensis, krusei, lusitaniae, albicans, tropicalis, glabrata and parapsilosis [ 30 ]. Oteseconazole carries a risk of embryo-fetal toxicity and is therefore not permitted for use in women with reproductive potential [ 31 , 32 ].

The synthetic method of oteseconazole was reported by Hoekstra, William J. and co-workers (Fig. 2 ) [ 33 ]. The cross-coupling reaction of ethyl bromodifluoroacetate (OTES-002) and 2, 5-dibromopyridine (OTES-001) in the presence of Cu powder in DMSO gives OTES-003. OTES-003 reacts with l-bromo-2,4-difluorobenzene (OTES-004) in methyl tert -butyl ether (MTBE), affording OTES-005, which is then subjected to epoxidation reaction in the presence of trimethyl sulfoxonium iodide (TMSOI) and potassium tert -butoxide to afford epoxide OTES-006. Subsequent addition reaction affords racemic OTES-007. Compound OTES-007 undergoes chiral resolution with di- p -toluoyl-L-tartaric acid (L-DPTTA) in the mix solvents of isopropanol and acetonitrile, followed by the treatment of trimethylsilyl azide, giving tetrazole OTES-009. Finally, OTES-009 undergoes Suzuki–Miyaura reaction with aryl boronic acid OTES-010 to provide coupling compound oteseconazole.

Synthesis of oteseconazole, vonoprazan and lenacapavir

Vonoprazan, amoxicillin, and clarithromycin (Voquezna)

Vonoprazan was first launched in Japan in February 2015 to treat acid-related diseases and as an adjunct to the eradication of Helicobacter pylori [ 34 , 35 , 36 ]. As a potassium-competitive acid blocker (PCAB), vonoprazan blocks the secretion of gastric acid mediated by H + , K + -ATPase, which can be regarded as an alternative to proton-pump inhibitors to treat acid-associated disorders. CYP2C19 genetic polymorphisms show little effect on PCABs, which is obviously different from proton-pump inhibitors [ 37 ]. In addition, vonoprazan exhibits 350 times more active than lansoprazole, a proton pump inhibitor, which is attributed to its ability to accumulation in the gastric corpus mucosa, especially in parietal cells [ 38 ]. In May 2022, Vonoprazan, in combination with clarithromycin and amoxicillin was approved to treat Helicobacter pylori infection [ 39 ]. These approvals are based on the safety and effectiveness data of phalcon-hp phase 3 trial, which is the largest registered trial ever conducted in the United States in Helicobacter pylori , and 1046 patients were randomly assigned [ 40 ]. In the improved intention to treat population, the two vonoprazan treatment regimens showed no worse than lansoprazole triple therapy in patients without clarithromycin or amoxicillin resistant Helicobacter pylori strains at baseline [ 41 ]. The combination of amoxicillin, vonoprazan and clarithromycin has been reported to result in an eradication rate of Helicobacter pylori of about 90% [ 42 , 43 ].

Among the synthetic methods of vonoprazan [ 44 , 45 , 46 ], a relatively simple method starting from pyridine-3-sulfonyl chloride (VONO-001) is exhibited in Fig. 2 [ 47 ]. Nucleophilic substitution of VONO-001 with 5-(2-fluorophenyl)-1 H -pyrrole-3-carbonitrile (VONO-002) gives VONO-003, which then undergoes Raney-Ni promoted reduction reaction to give amine VONO-004. The resulting product VONO-004 is treated with paraformaldehyde and NaBH 4 generating the desired vonoprazan.

Lenacapavir (Sunlenca)

Lenacapavir, a first-in-class picomolar inhibitor of HIV-1 capsid protein, is used as a monotherapy, featuring little cross-resistance with clinically used antiretroviral agents and extended pharmacokinetics [ 48 , 49 ]. The European Commission granted the first worldwide approval of Lenacapavir to treat adults with multidrug-resistant HIV infection on 22 August 2022. On December 22, 2022, it also received FDA approval to treat HIV patients [ 50 , 51 ]. Lenacapavir exhibits its anti-HIV-1 activity through blocking the viral replication of HIV-1 virus, which is closely related to many processes of viral lifecycle: uptake, assembly, and release [ 52 ]. The lenacapavir's difluorobenzyl ring and CPSF6/Nup153 share the same binding pocket, with the benzyl groups of F1417 and F321 overlapping [ 53 ]. The crystal structure reveals that six lenacapavir molecules establishes a wide range of interactions with the protein, including cation-π interactions, hydrophobic interactions, and hydrogen bonds, thereby interrupting capsid interactions with CPSF6 and Nup153. In multiple cell lines, in vitro HIV-1 replication inhibition assays show EC 50 values of ~ 12–314 pM. Lenacapavir exhibits different inhibitory effect at low and high concentrations: it blocks viral nuclear entry at 0.5 nM, while inhibits the reverse transcription and DNA synthesis at 5–50 nM [ 54 ].

The process route of lenacapavir is described below in Fig. 2 [ 55 ]. The sequence begins with acetylation of commercial 2,5-dibromopyridine (LENA-001) with DMF. This is followed by the condensation with diphenylmethanamine (LENA-004) to access the imine LENA-005. Next, LENA-005 is reacted with 1-(bromomethyl)-3,5-difluorobenzene (LENA-006) affording LENA-007, which is converted to the amine LENA-008 through N -deprotection. Racemic LENA-008 undergoes chemical resolution upon treatment with ( R )-2-hydroxy-2-phenylacetic acid (LENA-009) to obtain single enantiomer salt LENA-010. Subjection of LENA-010 and 3-methyl-3-(methylsulfonyl)but-1-yne (LENA-011) to Sonogashira coupling conditions generates the alkyne LENA-012, and this is followed by condensation with the carboxylic acid LENA-013 in base to provide the amide LENA-014. Suzuki reaction of LENA-014 with the borate ester LENA-015 produces the coupling compound LENA-016. This salt is then removed crystalline alcohol through NaOH followed by nucleophilic substitution with methanesulfonyl chloride yielding LENA-018 with two methanesulfonyl groups. Sequential removal of one of methanesulfonyl group and acidification produce lenacapavir.

Central nervous system drugs

Daridorexant (quviviq).

Daridorexant, the second orexin receptor antagonist after suvorexant, was approved by the FDA on January 10, 2022, for clinical use to treat adult insomnia patients with difficulties of sleep maintenance and/or sleep onset [ 56 , 57 ]. It was then approved by the European Commission on 3 May 2022, making it the first dual orexin receptor antagonist to be approved for marketing [ 58 ]. Daridorexant potently inhibits orexins by working on OX1R and OX2R (Ki = 0.47 and 0.93 nM, respectively), which are wake-promoting endogenous ligands and neuropeptides [ 59 ]. Daridorexant is found to decrease overactive wakefulness. Daridorexant has been reported to improve daytime functioning and sleep in insomnia patients [ 60 ]. Before the approval of daridorexant, two orexin receptor antagonists have been marketed, including Mercer's suvorexant (approved in 2014) and Eisai's lemborexant (approved in 2019) [ 61 ]. But neither has fared well in the market so far.

The synthesis of daridorexant is outlined in Fig. 3 [ 62 ]. 2-Methyl-L-proline hydrochloride (DARI-001) is treated with di- tert -butyl pyrocarbonate (Boc 2 O) in 1/1 mixture solvents of MeCN and water, giving N -Boc protection product DARI-002. Treatment of DARI-002 with 6-chloro-2,3-diaminotoluene (DARI-003) under condensation reaction conditions furnishes amide DARI-004. Next, intramolecular condensation of DARI-004 under 100 °C provides DARI-005, which then undergoes N -Boc deprotection and condensation with 5-methoxy-2-(2 H -1,2,3-triazol-2-yl)benzoic acid (DARI-007) to provide daridorexant.

Synthesis of daridorexant, ganaxolone, and taurursodiol

Ganaxolone (Ztalmy)

Developed by Marinus, Ganaxolone was granted FDA approval as the inaugural treatment specifically indicated for seizures in cyclin-dependent kinase-like 5 deficiency disorder (CDD) [ 63 , 64 ]. Ganaxolone is one of the metabolites of progesterone from 3β-methylation of allopregnanolone [ 63 ]. Ganaxolone, a new class of neuroactive steroids, is effective positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors [ 65 ], which has specific and potent efficacy, like its endogenous counterparts [ 66 ]. Ganaxolone exerts its effect by binding to one specific allosteric binding site of GABAA, which is different from that of benzodiazepine [ 67 ]. It is characterized by analgesic, sedative, anxiolytic, hypnotic, anticonvulsant, and anesthetic properties [ 68 ]. It is important to note that antiepileptic medications may increase the risk of suicidal ideation and suicidal behavior, and caution should be taken when considering treatment with ganaxolone [ 69 , 70 , 71 ].

To this day, several synthetic methods of ganaxolone have been reported [ 72 , 73 , 74 ], one representative approach is depicted in Fig. 3 [ 72 ]. Starting with pregnenolone (GANA-001), reduction of double bond with hydrogen catalyzed by Pd/C affords compound GANA-002. The subsequent oxidation reaction of GANA-002 with NaOCl and NaBr gives diketone GANA-003, followed by epoxidation reaction to provide epoxide GANA-004. Finally, GANA-004 undergoes NaI promoted ring-opening producing ganaxolone.

Sodium phenylbutyrate/taurursodiol (Relyvrio)

Phenylbutyric acid, a fatty acid derivative of butyric acid produced by natural fermentation of colon bacteria, has many cellular and biological effects, such as easing inflammation, which is used to treat neurological or urea cycle disorders and inherited metabolic syndrome [ 75 ]. Sodium phenylbutyrate is a prodrug of phenylacetic acid that quickly metabolizes to its original style [ 76 ]. Then, phenylacetate binds to phenylacetyl-CoA, which is subjected to acetylation to give phenylacetylglutamine, which is ultimately excreted by the kidneys [ 77 ]. In Europe, taurursodiol, a taurine conjugate of ursodeoxycholic acid, is utilized for the prevention and treatment of gallstones due to its antiapoptotic and inhibitory effects on ER stress response [ 78 ]. Furthermore, taurursodiol has been also investigated in neurodegenerative and inflammatory metabolic diseases due to its array of molecular properties, such as anti-apoptotic effects [ 79 , 80 ]. Taurursodiol effectively decreases the body cholesterol content and intake of dietary cholesterol by reducing intestinal absorption of cholesterol [ 81 ]. Relyvrio, an FDA-approved treatment for amyotrophic lateral sclerosis (ALS), is a blend of sodium phenylbutyrate and taurursodiol [ 82 , 83 ]. ALS is so deadly that most patients have a life expectancy of only 3 to 5 years after onset of symptoms, and they typically die from respiratory failure, a progressive atrophy of the muscles used for respiration [ 84 , 85 , 86 , 87 ]. Relyvrio received early FDA approval due to the highly progressive nature and serious threat of ALS. However, Relyvrio prolong patients’ survival by slowing progression but not cure disease [ 88 , 89 ].

The synthesis of taurursodiol was disclosed by Sandhill One, LLC in 2022 (Fig. 3 ) [ 90 ]. Condensations of 3-ketochol-4-enoic acid (TAUR-001) with 2,2-dimethyl-1,3-propanediol (TAUR-002) and MeOH in the presence of p -toluenesulfonic acid (TsOH), giving TAUR-003. Subsequent hydroxylation and oxidation with NHPI ( N -hydroxyphthalimide) and pyridinium dichromate (PDC) form TAUR-004. Next, TAUR-004 is reduced with H 2 , followed by oxidation with pyridinium chlorochromate (PCC) to provide TAUR-005 over two steps. Treatment of compound TAUR-005 with HCOOH provides TAUR-006, in which the carbonyl is deprotected. One of the carbonyls of TAUR-006 then undergoes reduction, and the ester group is hydrolyzed at the same time, giving TAUR-007. After reduction of the other carbonyl, compound TAUR-008 reacts with taurine sodium salt (TAUR-009), giving taurursodiol.

Dermatologic drugs

Abrocitinib (cibinqo).

On December 10, 2021, abrocitinib was initially approved by the European Commission to treat adult patients with atopic dermatitis (AD) [ 91 , 92 ]. On January 14, 2022, abrocitinib received the FDA approval to treat patients with refractory moderate-to-severe AD who have limited or little response to other systemic drugs [ 93 ]. Abrocitinib potently and selectively inhibits JAK1 with an IC 50 value of 29 nM, which is better than that of JAK2 (IC 50 = 803 nM). Abrocitinib exerts anti-inflammatory effects by blocking pro-inflammatory cytokine signaling associated with atopic dermatitis [ 94 ]. It effectively decreases serum markers of atopic dermatitis inflammation in a dose-dependent manner, including interleukin-31 (IL-31), thymus and activation-regulated chemokine (TARC), and high-sensitivity C-reactive protein (hsCRP) [ 95 ]. Mean absolute lymphocyte counts increased during two weeks of treatment and returned to baseline after 9 months of treatment [ 93 , 96 , 97 ]. According to the Phase 3 results, the experimental group showed significant improvement in disease extent, severity, and skin clarity compared to the placebo group, and patients were able to rapidly relieve itching symptoms after two weeks treatment [ 94 ]. It is one of the first oral JAK inhibitors for AD in the United States, and previously received FDA breakthrough treatment and priority review qualifications [ 98 ].

Several synthetic methods of abrocitinib have been reported [ 95 , 99 , 100 , 101 , 102 , 103 ], one representative synthetic route is described in Fig. 4 [ 104 ]. Curtius rearrangement and addition of 3-oxocyclobutane-1-carboxylic acid (ABRO-001) with phenylmethanol (ABRO-002) give ABRO-003 [ 105 ]. Next, treatment of compound ABRO-003 with monomethylamine in acetic acid, which then undergoes NaBH 4 -catalyzed reduction reaction to provide chiral compound ABRO-004. Treatment of ABRO-004 with pyrimidine ABRO-005 in the presence of K 2 CO 3 provides the corresponding substitution product ABRO-006, followed by dechlorination and hydrolysis, giving salt ABRO-007. Finally, treatment of ABRO-007 with propane-1-sulfonyl chloride (ABRO-008) provides nucleophilic substitution product abrocitinib.

Synthesis of abrocitinib, tapinarof and deucravacitinib

Tapinarof (Vtama)

Tapinarof was approved by FDA on May 23, 2022, to treat plaque psoriasis [ 106 , 107 ]. Tapiranof was originally identified as a metabolite (3, 5-dihydroxy-4-isopropyl styrenes) generated by Photorhabdus luminescens, a species of gram-negative bacilli living together with allogenic nematodes [ 108 ]. As a first-in-class agonist of aryl hydrocarbon receptor (AhR), Tapinarof exhibits excellent potency toward AhR (EC 50 = 13 nM), which effectively regulates antioxidant activity and skin barrier protein expression, and inhibits inflammatory cytokines [ 109 ]. Tapinarof directly binds to AhR, thereby activating the AhR pathway. Tapinarof induces AhR nuclear translocation in immortalized keratinocytes (HaCaT) in a dose-dependent manner (EC 50 = 0.16 nM). The anti-inflammatory effect of tapinarof may be due to Nrf2, a downstream effector of AhR, but not all AhR agonists can activate the pathway [ 110 ]. Therefore, the dual AhR/Nrf2 action of tapinarof may be responsible for psoriasis therapy [ 111 ].

The total synthesis of tapinarof is depicted in Fig. 4 [ 112 ]. Methylation of commercially available dimethyl sulfate with 3,5-dihydroxybenzoic acid (TAPI-001), followed by reaction with isopropyl alcohol in the presence of 60% ~ 80% concentrated sulfuric acid, giving TAPI-003. Subsequently reduction of carboxyl forms alcohol TAPI-004. Next, chlorination of TAPI-004 with hydrochloric acid provides TAPI-005, which then undergoes Wittig-Horner condensation to generate compound TAPI-006. TAPI-006 reacts with benzaldehyde in the presence of NaH and THF under nitrogen atmosphere, affording TAPI-007, which is subjected to demethylation catalyzed by pyridine hydrochloride to afford the target compound tapinarof.

Deucravacitinib (Sotyktu)

On September 9, 2022, Deucravacitinib was approved by the FDA to treat moderate-to-severe plaque psoriasis [ 113 ]. Deucravacitinib, a member of the Janus kinase (JAK) family, is a highly potent allosteric inhibitor of tyrosine kinase 2 (TYK2) with an IC 50 value of 1.0 nM [ 114 ]. It stabilizes an inhibitory interaction between catalytic and regulatory domains of the enzyme, which blocks the activation of Signal Transducers and Activators of Transcription (STATs) and TYK2in cell-based assays [ 115 , 116 , 117 ]. The precise mechanism by which inhibiting the TYK2 enzyme leads to effective treatment in patients with moderate-to-severe plaque psoriasis is still not fully understood. However, its mechanism is different from other Janus kinase inhibitors targeting the conserved active domain, thereby exerting its high selectivity toward TYK2 [ 118 ], which is expected to avoid various adverse effects caused by non-selective JAK inhibitors, such as kidney and liver dysfunction, and altered triglyceride and cholesterol level.

Preparation of deucravacitinib is outlined in Fig. 4 [ 119 ]. Chlorodehydration of 4,6-dihydroxypyridazine-3-carboxylate (DEUC-001) with phosphorus oxychloride affords the corresponding dichloride DEUC-002, which undergoes hydrolysis in the presence of lithium bromide and Hunig’s base in aqueous acetonitrile to yield the lithium carboxylate DEUC-003. Nucleophilic aromatic substitution with DEUC-004 takes place at C4 position of DEUC-003, in the presence of zinc acetate, leading to the formation of DEUC-005 as a zinc salt. Subsequent coupling with cyclopropanecarboxamide (DEUC-006) is catalyzed by palladium acetate and a Josiphos ligand to generate compound DEUC-007. Finally, DEUC-007 undergoes an amidation with methan-d 3 -amine hydrochloride in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) and N -methylimidazole (NMI), affording deucravacitinib.

Hematologic drugs

Mitapivat (pyrukynd).

Mitapivat is the first orally active pyruvate kinase allosteric activator, which was approved by FDA on February 17, 2022, to manage hemolytic anemia in individuals with pyruvate kinase (PK) deficiency [ 120 , 121 , 122 ]. Mitapivat activates PK through allosteric regulation, binding to a distinct allosteric site on the PKR tetramer separate from fructose bisphosphate FBP [ 123 ]. The red blood cell (RBC) form of PK is mutated in PK deficiency, resulting in shortened RBC lifespan, reduced adenosine triphosphate (ATP), and chronic hemolysis [ 124 ]. Mitapivat increases its affinity for its substrate and stabilizes phosphoenolpyruvate by binding to pyruvate kinase [ 120 ]. Mitapivat increases ATP production and erythrocyte pyruvate kinase activity (wild-type and mutant forms) but reduces levels of 2,3-DPG [ 123 ]. Mitapivat has also been investigated in other genetic disorders affecting red blood cells and causing hemolytic anemia, such as α-/β-thalassemia and sickle cell disease [ 123 ].

The preparation of mitapivat developed by Agios is shown in Fig. 5 [ 125 , 126 ]. Starting with ethyl 4-aminobenzoate (MITA-001), a nucleophilic substitution reaction with quinoline-8-sulfonyl chloride (MITA-002), followed by NaOH promoted hydrolysis, giving MITA-004. Finally, the condensation of MITA-004 with 1-(cyclopropylmethyl)piperazine (MITA-005) in the presence of 1,1'-carbonyldiimidazole (CDI) gives the desired mitapivat.

Synthesis of mitapivat and pacritinib

Pacritinib (Vonjo)

On February 28, 2022, the FDA granted accelerated approval to Pacritinib, a highly effective inhibitor of JAK2 and FMS-like tyrosine kinase 3 (FLT3), which was used to treat adult patients with low platelets who suffer from intermediate or high-risk primary or secondary myelofibrosis (MF) [ 127 , 128 ]. Pacritinib potently inhibits wild-type JAK2 (IC 50 = 23 nM), JAK2 V617F (IC 50 = 19 nM), FLT3 (IC 50 = 22 nM), and FLT3 D835Y (IC 50 = 6 nM) [ 129 ], which benefits the signaling of many growth factors and cytokines associated with immune and hematopoiesis function. MF is closely related to dysregulated JAK2 signaling. Pacritinib carries significant selectivity for JAK2 over JAK3 and TYK2, and does not inhibit JAK1 at clinically relevant concentrations [ 130 ].

Pacritinib demonstrates a dose-dependent suppression of signal transducer and activator of transcription 5 (STAT5) phosphorylation in expanded erythroid progenitor cells obtained from healthy individuals [ 131 ]. A single 400 mg dose of pacritinib moderately inhibits STAT3 phosphorylation induced by interleukin 6 in the whole blood of healthy subjects [ 132 , 133 ]. Pacritinib is administered orally twice daily and is contraindicated in patients with renal insufficiency and hepatic insufficiency. It offers an alternative for MF patients with severe thrombocytopenia, commonly carrying a pretty poor prognosis [ 134 ].

Although several synthetic routes to pacritinib have been reported [ 135 , 136 ], an efficient approach has been disclosed in Fig. 5 [ 137 ]. Substitution of 3-(2-chloropyrimidin-4-yl)benzaldehyde (PACR-001) with 5-amino-2-(2-chloroethoxy)benzaldehyde (PACR-002), followed by N -Boc protection of compound PACR-003 with di- tert -butyl pyrocarbonate, generating the key intermediate PACR-004. Further NaBH 4 promoted reduction of PACR-004 furnishes PACR-005. Treatment of PACR-005 with ( E )-1,4-dibromobut-2-ene (PACR-006) in basic solution gives the ring-closing product PACR-007, which undergoes nucleophilic substitution reaction with pyrrolidine (PACR-008) to provide the desired pacritinib.

Oncologic drugs

Lutetium ( 177 lu) vipivotide tetraxetan (pluvicto).

As a radioligand therapeutic agent, lutetium ( 177 Lu) vipivotide tetraxetan consists of a radionuclide, lutetium Lu-177, conjugated to a prostate-specific membrane antigen (PSMA)-binding moiety, exercising cytotoxic effect on cancer cells [ 138 , 139 ]. The β-negative emission of lutetium Lu-177 irradiates PSMA-expressing cells and surrounding cells, thereby inducing DNA damage and cell death. In a clinical trial, it was discovered that Lutetium ( 177 Lu) vipivotide tetraxetan exhibited a significant correlation with an 80.4% decrease in serum PSA levels. Additionally, the median progression-free survival for these patients was determined to be 13.7 months [ 140 ]. Following other therapies, it was granted FDA approval on March 23, 2022, to treat metastatic castration-resistant prostate cancer with prostate-specific membrane antigen positivity [ 141 ]. This approval is based on the positive results of phase 3 clinical trial, which showed that the addition of Pluvicto reduced the risk of patient death by 38% compared to standard therapy and that Pluvicto also significantly reduced the risk of patients developing radiographic disease progression or death [ 142 ]. Furthermore, in patients with evaluable disease at baseline, the overall remission rate was 30% in the Pluvicto group, compared to 2% in the standard treatment control group [ 143 ]. In October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a recommendation for the authorization of marketing for a therapeutic intervention targeting prostate cancer [ 144 ].

Preparation of lutetium ( 177 Lu) vipivotide tetraxetan is depicted in Fig. 6 [ 145 , 146 ]. Starting from 2-chlotrotrityl chloride (2-CT) resin, installation of LUTE-001 is accomplished in the presence of DCM to furnish LUTE-002. From LUTE-002, condensation with isocyanic acid LUTE-003 provides the intermediate LUTE-004. Treatment of LUTE-004 with Pd[P(C 6 H 5 ) 3 ] 4 and morpholine, followed by condensation with Fmoc-L-2-NaI-OH, forming LUTE-006. Following the same procedure, LUTE-007 is synthesized. Further condensation and radiolabelling with 177 Lu give Lutetium ( 177 Lu) vipivotide tetraxetan.

Synthesis of lutetium ( 177 Lu) vipivotide tetraxetan, futibatinib and olutasidenib

Futibatinib (Lytgobi)

On September 30, 2022, the FDA granted approval to Futibatinib, a permanent inhibitor of Fibroblast Growth Factor receptor (FGFR), for the treatment of intrahepatic cholangiocarcinoma that contains FGFR2 gene fusions or other genetic rearrangements [ 147 ]. Futibatinib effectively inhibits FGFR 1–4 (IC 50 = 3.9, 1.3, 1.6, and 8.3 nM), respectively, by forming a covalent bond with cysteine in the ATP-binding pocket of FGFR kinase domain [ 148 , 149 , 150 ]. In addition, Futibatinib exhibits similar inhibitory potency toward wild-type (WT) and mutant FGFR2 with IC 50 values of 0.9 nM, 1–3 nM, 3.6 nM, and 2.4 nM against WT FGFR2, V5651, N550H, and E566G, respectively [ 148 , 149 , 150 ]. FGFR plays a crucial role in cell differentiation, survival, proliferation, and migration, and aberrant signaling pathways and genomic aberrations commonly occur in a variety of cancers since the survival and proliferation of malignant cells can be supported by FGFR signaling [ 148 , 151 ]. Futibatinib efficiently inhibits the phosphorylation of FGFR and subsequent signaling pathways. This inhibition leads to a decrease in the survival of cancer cells harboring FGFR rearrangements, fusions, mutations, and amplifications in xenograft models derived from mice and rats [ 152 ]. In the end, futibatinib effectively decreases the survival of cancer cells with FGFR alterations, such as FGFR fusions or rearrangements, amplifications, and mutations [ 153 ].

Futibatinib is prepared as described in Fig. 6 [ 154 ]. Sonogashira coupling between FUTI-001 and l-ethynyl-3,5-dimethoxybenzene (FUTI-002) gives compound FUTI-003, followed by the treatment of FUTI-003 with 3-chloropropionyl chloride (FUTI-004), affording the product futibatinib.

Olutasidenib (Rezlidhia)

On December 1, 2022, the FDA granted approval to olutasidenib, a highly effective inhibitor of isocitrate dehydrogenase-1 (IDH1), to treat relapsed or refractory acute myeloid leukemia (AML) in adults who possess a susceptible IDH1 mutation [ 155 , 156 ]. Normally, IDH1 catalyzes mediated the conversion of isocitrate to α-ketoglutarate (α-KG) through oxidative decarboxylation reaction [ 157 ]. However, IDH1 mutations are commonly observed in the catalytic sites of arginine in various cancers, such as AML, and stimulate the transfer of α-KG to 2-hydroxyglutarate (2-HG) [ 158 ]. This leads to 2-HG increase, which is closely related to the inhibition of α-KG-dependent mechanisms, such as collagen synthesis, epigenetic regulation, and cell signaling. Olutasidenib effectively decreases 2-HG levels by selectively targeting mutant IDH1, leading to the restoration of normal cell differentiation and offering therapeutic advantages in IDH1 mutant strains. Additionally, olutasidenib is currently investigated to treat myelodysplastic syndromes (MDS), as well as solid tumors and gliomas (NCT03684811) [ 159 , 160 , 161 ].

The synthetic route of olutasidenib as described in the publication is shown in Fig. 6 [ 162 ]. N -oxidation of commercially available 5-fluoropicolinonitrile (OLUT-001) followed by reflux of the N -oxide (OLUT-002) in acetic anhydride give the acetate OLUT-003. Base-mediated hydrolyzation and tautomerism of OLUT-003, followed by N -methylation with methyl iodide provide N -methylated compound OLUT-005. Finally, the condensation of OLUT-005 with the amine OLUT-006 affords olutasidenib.

Of note, the preparation of the amine OLUT-006 arises from commercially available quinoline aldehyde OLUT-007, which is first condensed with ( R )- tert -butanesulfinamide (OLUT-008) to obtain the chiral ( R )- N - tert -butanesulfinimine (OLUT-009) in 81% yield (Fig. 7 ). Next, an addition reaction of OLUT-009 and methylmagnesium bromide in dichloromethane is employed to yield the intermediate OLUT-010 as the major diastereoisomer (98:2 dr). Removal of the sulfonyl group using hydrochloric acid provides the intermediate OLUT-006 in quantitative yield.

Synthesis of adagrasib, mavacamten and terlipressin

Adagrasib (Krazati)

Adagrasib, an orally bioavailable inhibitor of KRAS, was developed by Mirati. On December 12, 2022, Therapeutics obtained accelerated FDA approval to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer in adults who have undergone at least one prior systemic therapy [ 163 , 164 , 165 ]. Normally, activation of KRAS through binding to guanosine triphosphate (GTP) stimulates the activation of intracellular signal transduction and MAP kinase pathway. Hydrolyzation of GTP gives guanosine diphosphate (GDP) and KRAS restores the inactive state [ 166 ]. Cysteine substitution of Gly12 in KRAS (KRASG12C) damages GTP hydrolysis and keeps KRAS in active form, which results in uncontrolled cell growth and proliferation as well as malignant transformation [ 167 ]. Adagrasib covalently and selectively binds to KRASG12C and locks it in the inactive state, thus exerting anti-tumor activity by inhibiting tumor cell viability and growth [ 168 ].

The synthesis of adagrasib begins by condensing ethyl 1-benzyl-3-oxopiperidine-4-carboxylate (ADAG-001) with urea. This reaction forms ADAG-002, which is a bicyclic diol. ADAG-002 is then chlorinated using POCl 3 to produce pyrimidine (ADAG-003) (Fig. 7 ) [ 169 ]. Next, treatment of intermediate ADAG-003 with sodium methoxide in methanol, followed by Buchwald coupling with ( S )-(1-methylpyrrolidin-2-yl)methanol (ADAG-005), gives compound ADAG-006. N -debenzylation of ADAG-006 in the presence of hydrogen catalyzed by Pd(OH)/C affords the amine ADAG-007, which is treated with 1-bromo-8-chloronaphthalene (ADAG-008) under Buchwald-Hartwig amination conditions to give the N -arylated product ADAG-009. Demethylation and subsequent triflate formation provide ADAG-011, which reacts with ( S )-2-(piperazin-2-yl)acetonitrile (ADAG-012) affording the advanced intermediate ADAG-013. It then undergoes ammonolysis with 2-fluoroacrylic acid using T3P as the coupling reagent to obtain adagrasib [ 170 ].

Other drugs

Mavacamten (camzyos).

Mavacamten was approved by US FDA in 2022, which is used to treat adult patients with obstructive hypertrophic cardiomyopathy (oHCM) who are experiencing symptoms and fall into New York Heart Association (NYHA) class II-III [ 171 , 172 ]. Mavacamten is a medication that can be taken by mouth. It acts as an inhibitor of cardiac myosin, which is a protein involved in muscle contraction in the heart. This medication works by regulating the number of myosin heads that can enter the "on actin" states, effectively reducing the likelihood of generating force during systole (contraction) and residual force during diastole (relaxation) across the bridge. Additionally, its inhibitory effects are reversible, meaning that its action can be reversed if necessary [ 173 ]. HCM is characterized by the presence of excessive formation of myosin actin bridges and dysregulation of the hyperrelaxation state [ 174 ]. Mavacamten transforms the total amount of myosin into an energy-saving, absorbable, ultra-relaxed state [ 175 ]. Inhibition of myosin with Mavacamten reduced dynamic left vein obstruction and improved cardiac filling pressure in patients with HCM. It has been reported that the IC 50 values of Mavacamten in the bovine, human, and rabbit system are 490 nM, 711 nM, and 2140 nM, respectively, indicating a 4-fold selectivity for myocardial myosin [ 176 , 177 , 178 ]. Mavakamten is found to reduce contractility through decreasing the activity of adenosine triphosphatase in the heavy chain of myocardial myosin [ 179 ]. Long-term administration results in the inhibition of the development of myocardial cell disorders, myocardial hypertrophy, and myocardial fibrosis, and attenuates the gene expression of profibrotic and hypertrophic in mice featuring heterozygous human mutations in the chain of myosin heavy [ 176 ].

A convenient synthetic method of mavacamten was disclosed in 2014 (Fig. 7 ) [ 180 ]. Addition of commercially available isopropylamine (MAVA-001) with trimethylsilyl isocyanate (MAVA-002), followed by the annulation reaction with dimethyl malonate in the presence of sodium methoxide and methanol, giving MAVA-003. Subsequently, chlorination forms compound MAVA-005. Finally, the coupling of MAVA-005 with ( S )-α-methylbenzylamine (MAVA-006) in dioxane under 90 °C provides desired mavacamten.

Terlipressin (Terlivaz)

Terlipressin, a medication aimed at enhancing kidney function in adult patients with hepatorenal syndrome experiencing a rapid decline in kidney function, obtained FDA approval on September 14, 2022 [ 181 , 182 ]. Terlipressin, an analog of vasopressin, is an endogenous neurohormone that acts as a vasoconstrictor [ 183 , 184 , 185 , 186 , 187 , 188 ]. As a prodrug of lysine-vasopressin, terlipressin itself is pharmacologically active, characterized by a longer half-life and higher selectivity for V1 receptor than vasopressin, which controls acute variceal bleeding, and reduces the splanchnic blood flow and portal pressure [ 189 ]. These favorable pharmacokinetic and molecular properties of terlipressin confer several advantages, such as convenience in patients with limited intravenous access and prevention of rebound hypotension upon discontinuation [ 188 , 190 ].

Preparation of terlipressin is described in Fig. 7 [ 191 ]. Condensation of thioester TERL-001 and N -terminal cysteine TERL-002 furnishes TERL-003 in the presence of 3-( N -morpholino)propanesulfonic (MOPS) and catalytic guanidine. Subsequent condensation of TERL-003 with Boc-Cys(trt)-OH TERL-004 and N -Boc deprotection furnish TERL-005, further guanidine-catalyzed condensation with TERL-006 gives TERL-007. Oxidation of TERL-007 in MeCN/H 2 O gives terlipressin.

Gadopiclenol (Elucirem)

Gadopiclenol, a gadolinium-based contrast agent (GBCA), was developed by Guerbet. On September 21, 2022, after undergoing a priority review, the FDA granted its approval to the product. Its primary objective is to identify and display abnormal vascularity lesions in the body and the central nervous system, in combination with magnetic resonance imaging (MRI). In 2006, linear GBCA use was linked to nephrogenic systemic fibrosis (NSF) [ 192 , 193 , 194 ], a rare disease characterized by hardening and thickening of the subcutaneous and skin tissue, which has not been detected in macrocyclic GBCAs, such as gadopiclenol [ 195 ]. It should be noted that in NSF patients with impaired drug clearance, a black box warning was given to gadopiclenol to remind an increased risk. Gadopiclenol carries two water molecule exchange sites for increased relaxation and contrast [ 195 ]. Compared with other non-specific GBCAs, gadopiclenol dose is only half of the conventional gadolinium dose, alleviating practitioners' concerns about radiation exposure [ 196 ]. Variations in radiofrequency signal strength allow visualization of normal and pathological tissue during MRI, which is characterized by the differences in longitudinal relaxation times (T1) or spin–lattice, proton density, or in transverse relaxation times or spin–spin (T2). The T1 and T2 relaxation times can be shortened by Gadopiclenol, resulting in the visualization of target tissues during MRI [ 197 ]. The extent of a contrast agent affecting the tissue water relaxation rate (1/T1 or 1/T2) is expressed in terms of the relaxation rate (r1 or r2). The high r1 relaxation rate and kinetic stability of gadopiclenol allow it to be used at lower doses than traditional extracellular GBCAs. What deserves special vigilance is that acute kidney injury and hypersensitivity reactions may also occur with gadopiclenol [ 198 ].

The reported synthesis of gadopiclenol was reported by Marc, in 2007 (Fig. 8 ) [ 199 ]. Treatment of compound GADO-001 with 3-aminopropyl-1,2-diol (GADO-002) in the presence of HOBt and EDC gives gadopiclenol.

Synthesis of gadopiclenol and omidenepag isopropyl

Omidenepag isopropyl (Omlonti)

Omidenepag isopropyl, approved in Japan in 2018 as a potent agonist of EP2 receptor to treat ocular hypertension and glaucoma [ 200 ], was then approved by FDA on September 22, 2022, to lower high intraocular pressure in individuals diagnosed with ocular hypertension or open-angle glaucoma. Omidenepag isopropyl is rapidly metabolized to its active metabolite omidenepag, which binds strongly to prostaglandin E2 (EP2) receptor (Ki = 3.6 nM) [ 201 ]. Furthermore, Omidenepag is highly agonistic at the EP2 receptor (EC 50 = 8.3 nM) but has little effect on other receptors such as prostaglandin E1 (EP1) or F receptors (FP) [ 200 , 202 , 203 ]. Unlike omidenepag, omidenepag isopropyl has little or no affinity for prostaglandin receptors [ 200 , 203 ]. EP2 receptor exists in different kinds of ocular tissues related to aqueous humor dynamics, such as ciliary muscle (CM) and trabecular meshwork (TM) [ 204 ]. Stimulation of EP2 receptors may result in increased intracellular cyclic adenosine monophosphate (cAMP), leading to relaxation of CM and TM tissues [ 205 ]. Omidenepag has shown comparable efficacy in lowering IOP to latanoprost, a prostaglandin FP receptor agonist, which is a first-line treatment for primary ocular hypertension and open-angle glaucoma [ 206 ].

Preparation of omidenepag isopropyl is depicted in Fig. 8 [ 202 ]. Treatment of OMID-001 with 1-(4-(bromomethyl)phenyl)-1 H -pyrazole (OMID-002) provides the corresponding coupling product OMID-003, followed by HCl-promoted hydrolysis and N -Boc deprotection, producing omidenepag. Esterification of omidenepag with isopropyl alcohol in dioxane yields omidenepag isopropyl.

Conclusion and prospect

In conclusion, in 2022, FDA approved 37 new drugs, including 20 NCEs, 7 monoclonal antibodies (mAbs), 3 bispecific antibodies (BsAbs), 2 enzymes, 1 fusion protein, 1 synthetic polypeptide, 1 small interfering RNA (siRNA), 1 toxin, 1contrast agent and a colony stimulating factor (CSF). In the context of the COVID-19 pandemic, FDA is still committed to supporting the development of rare disease drugs. The field of anti-tumor is still a hot area for innovative drug development. These approved new drugs will benefit patients suffering from orphans, cancer, nervous system diseases, infectious diseases, and many other diseases.

In this review, we summarized the clinic application and synthetic routes of the 19 NCEs of new drugs approved by the FDA. The pharmacophore library will be enriched and new drug discovery will be benefited by the presence of privileged scaffolds in these drug molecules. For example, me-better drug omidenepag isopropyl is developed based on the molecular structure of CP-533,536, which was reported by previous researchers and optimized through the structural modification of PGE2 [ 202 ]. The AIDS prevention drug lenacapavir is developed based on the structure of PF-3450074. In order to block the unstable metabolic site, researchers focused on introducing electron-withdrawing groups (halogens and sulfonyl groups) and metabolically stable rigid ring systems (cyclopropane and pyrazole) through optimization [ 207 ]. Both deucravacitinib and olutasidenib were first screened through high-throughput screening to obtain lead compounds, and their solubility was improved through SBDD. Adagrasib has increased its in vitro stability in whole blood (WB) by introducing a fluorine atom at the 2-position of acrylamide [ 208 ].

In addition, we discovered that metal-catalyzed coupling reactions were utilized in the synthesis of pharmaceuticals (such as omidenepag, futibatinib, oteseconazole, etc.). Chiral resolution and asymmetric synthesis were employed for obtaining the single enantiomer of the chiral drugs (such as taurursodiol, ganaxolone, and oteseconazole, etc.). Other traditional organic synthetic strategies, such as substitution reaction, hydrolysis reaction, Curtius rearrangement, and addition reaction were still used for the synthesis of these new drug molecules approved by the FDA. The special skeletons in the drug molecules enrich the effective pharmacophores, which will help to design new drugs.

Availability of data and materials

Not applicable.

Mullard A. 2022 FDA approvals. Nat Rev Drug Discov. 2023;22(2):83–8. https://doi.org/10.1038/d41573-023-00001-3 .

Article CAS PubMed Google Scholar

Food and Drug Administration. Novel Drug Approvals for 2022. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2022 . Accessed Dec 31, 2022.

Al-Madhagi HA. FDA-approved drugs in 2022: A brief outline. Saudi Pharm J. 2023;31(3):401–9. https://doi.org/10.1016/j.jsps.2023.01.007 .

Article CAS PubMed PubMed Central Google Scholar

Gabbard AP, Booth GS. Cold agglutinin disease. Clin Hematol Int. 2020;2(3):95–100. https://doi.org/10.2991/chi.k.200706.001 .

Article PubMed PubMed Central Google Scholar

Dhillon S. Sutimlimab: First approval. Drugs. 2022;82(7):817–23. https://doi.org/10.1007/s40265-022-01711-5 .

Tefferi A. The forgotten myeloproliferative disorder: Myeloid metaplasia. Oncologist. 2003;8(3):225–31. https://doi.org/10.1634/theoncologist.8-3-225 .

De SK. First approval of pacritinib as a selective janus associated kinase-2 inhibitor for the treatment of patients with myelofibrosis. Anticancer Agents Med Chem. 2023;23(12):1355–60. https://doi.org/10.2174/1871520623666230320120915 .

Hawkins PN, Ando Y, Dispenzeri A, Gonzalez-Duarte A, Adams D, Suhr OB. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015;47(8):625–38. https://doi.org/10.3109/07853890.2015.1068949 .

Keam SJ. Vutrisiran: First approval. Drugs. 2022;82(13):1419–25. https://doi.org/10.1007/s40265-022-01765-5 .

Ding HX, Leverett CA, Kyne RE, Liu KK, Fink SJ, Flick AC, et al. Synthetic approaches to the 2013 new drugs. Bioorg Med Chem. 2015;23(9):1895–922. https://doi.org/10.1016/j.bmc.2015.02.056 .

Flick AC, Ding HX, Leverett CA, Kyne RE, Liu KK, Fink SJ, et al. Synthetic approaches to the 2014 new drugs. Bioorg Med Chem. 2016;24(9):1937–80. https://doi.org/10.1016/j.bmc.2016.03.004 .

Flick AC, Ding HX, Leverett CA, Kyne RE, Liu KK, Fink SJ, et al. Synthetic approaches to the new drugs approved during 2015. J Med Chem. 2017;60(15):6480–515. https://doi.org/10.1021/acs.jmedchem.7b00010 .

Flick AC, Ding HX, Leverett CA, Fink SJ, O’Donnell CJ. Synthetic approaches to new drugs approved during 2016. J Med Chem. 2018;61(16):7004–31. https://doi.org/10.1021/acs.jmedchem.8b00260 .

Flick AC, Leverett CA, Ding HX, McInturff E, Fink SJ, Helal CJ, et al. Synthetic approaches to the new drugs approved during 2017. J Med Chem. 2019;62(16):7340–82. https://doi.org/10.1021/acs.jmedchem.9b00196 .

Flick AC, Leverett CA, Ding HX, McInturff E, Fink SJ, Helal CJ, et al. Synthetic approaches to new drugs approved during 2018. J Med Chem. 2020;63(19):10652–704. https://doi.org/10.1021/acs.jmedchem.0c00345 .

Yuan S, Yu B, Liu HM. New drug approvals for 2019: Synthesis and clinical applications. Eur J Med Chem. 2020;205:112667. https://doi.org/10.1016/j.ejmech.2020.112667 .

Flick AC, Leverett CA, Ding HX, McInturff E, Fink SJ, Mahapatra S, et al. Synthetic approaches to the new drugs approved during 2019. J Med Chem. 2021;64(7):3604–57. https://doi.org/10.1021/acs.jmedchem.1c00208 .

Yuan S, Luo YQ, Zuo JH, Liu H, Li F, Yu B. New drug approvals for 2020: Synthesis and clinical applications. Eur J Med Chem. 2021;215:113284. https://doi.org/10.1016/j.ejmech.2021.113284 .

Flick AC, Leverett CA, Ding HX, McInturff EL, Fink SJ, Mahapatra S, et al. Synthetic approaches to the new drugs approved during 2020. J Med Chem. 2022;65(14):9607–61. https://doi.org/10.1021/acs.jmedchem.2c00710 .

Yuan S, Wang DS, Liu H, Zhang SN, Yang WG, Lv M, et al. New drug approvals for 2021: Synthesis and clinical applications. Eur J Med Chem. 2023;245(Pt 1):114898. https://doi.org/10.1016/j.ejmech.2022.114898 .

Hoy SM. Oteseconazole: First approval. Drugs. 2022;82(9):1017–23. https://doi.org/10.1007/s40265-022-01734-y .

Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol. 2016;214(1):15–21. https://doi.org/10.1016/j.ajog.2015.06.067 .

Article PubMed Google Scholar

Garvey E, Hoekstra W, Moore W, Schotzinger R, Long L, Ghannoum M. VT-1161 dosed once daily or once weekly exhibits potent efficacy in treatment of dermatophytosis in a guinea pig model. Antimicrob Agents Ch. 2015;59(4):1992–7. https://doi.org/10.1128/AAC.04902-14 .

Article CAS Google Scholar

Warrilow A, Hull C, Parker J, Garvey E, Hoekstra W, Moore W, et al. The clinical candidate VT-1161 is a highly potent inhibitor of Candida albicans CYP51 but fails to bind the human enzyme. Antimicrob Agents Ch. 2014;58(12):7121–7. https://doi.org/10.1128/AAC.03707-14 .

De SK. Oteseconazole: First approved orally bioavailable and selective CYP51 inhibitor for the treatment of patients with recurrent vulvovaginal candidiasis. Curr Med Chem. 2023;30(37):4170–5. https://doi.org/10.2174/0929867330666230220130024 .

Sobel JD, Nyirjesy P. Oteseconazole: An advance in treatment of recurrent vulvovaginal candidiasis. Future Microbiol. 2021;16(18):1453–61. https://doi.org/10.2217/fmb-2021-0173 .

Chang YL, Yu SJ, Heitman J, Wellington M, Chen YL. New facets of antifungal therapy. Virulence. 2017;8(2):222–36. https://doi.org/10.1080/21505594.2016.1257457 .

Sun G, Thai SF, Lambert GR, Wolf DC, Tully DB, Goetz AK, et al. Fluconazole-induced hepatic cytochrome P450 gene expression and enzymatic activities in rats and mice. Toxicol Lett. 2006;164(1):44–53. https://doi.org/10.1016/j.toxlet.2005.11.015 .

Mast N, Zheng W, Stout CD, Pikuleva IA. Antifungal azoles: Structural insights into undesired tight binding to cholesterol-metabolizing CYP46A1. Mol Pharmacol. 2013;84(1):86–94. https://doi.org/10.1124/mol.113.085902 .

de Oliveira HC, Bezerra BT, Rodrigues ML. Antifungal development and the urgency of minimizing the impact of fungal diseases on public health. ACS Bio Med Chem Au. 2023;3(2):137–46. https://doi.org/10.1021/acsbiomedchemau.2c00055 .

Sobel JD. Candida vulvovaginitis: Treatment. https://medilib.ir/uptodate/show/115170 . Accessed Dec 20, 2022.

Martens MG, Maximos B, Degenhardt T, Person K, Curelop S, Ghannoum M, et al. Phase 3 study evaluating the safety and efficacy of oteseconazole in the treatment of recurrent vulvovaginal candidiasis and acute vulvovaginal candidiasis infections. Am J Obstet Gynecol. 2022;227(6):880.e1-880.e11. https://doi.org/10.1016/j.ajog.2022.07.023 .

Hoekstra WJ, Yates CM, Behnke M, Alimardanov A, David SA, Fry DF. Preparation of an antifungal tetrazole compound. 2015. WO2015143172A1.

Google Scholar

Garnock-Jones KP. Vonoprazan: First global approval. Drugs. 2015;75(4):439–43. https://doi.org/10.1007/s40265-015-0368-z .

Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002;347(15):1175–86. https://doi.org/10.1056/NEJMra020542 .

Suzuki S, Kusano C, Horii T, Ichijima R, Ikehara H. The ideal Helicobacter pylori treatment for the present and the future. Digestion. 2022;103(1):62–8. https://doi.org/10.1159/000519413 .

Echizen H. The first-in-class potassium-competitive acid blocker, vonoprazan fumarate: Pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet. 2016;55(4):409–18. https://doi.org/10.1007/s40262-015-0326-7 .

Sugano K. Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: Safety and clinical evidence to date. Therap Adv Gastroenterol. 2018;11:1756283X17745776. https://doi.org/10.1177/1756283x17745776 .

Vandecruys P, Baldewijns S, Sillen M, Van Genechten W, Van Dijck P. Oteseconazole: a long-awaited diversification of the antifungal arsenal to manage recurrent vulvovaginal candidiasis (RVVC). Expert Rev Anti Infect Ther. 2023;21(8):799–812. https://doi.org/10.1080/14787210.2023.2233696 .

Chey WD, Mégraud F, Laine L, López LJ, Hunt B, Smith N, et al. S1382 vonoprazan dual and triple therapy for Helicobacter pylori eradication. Am J Gastroenterol. 2021;116:S634. https://doi.org/10.14309/01.ajg.0000779060.18666.73 .

Article Google Scholar

Roque-Borda CA, Da Silva PB, Rodrigues MC, Di Filippo LD, Duarte JL, Chorilli M, et al. Pharmaceutical nanotechnology: Antimicrobial peptides as potential new drugs against WHO list of critical, high, and medium priority bacteria. Eur J Med Chem. 2022;241:114640. https://doi.org/10.1016/j.ejmech.2022.114640 .

Kiyotoki S, Nishikawa J, Sakaida I. Efficacy of vonoprazan for Helicobacter pylori eradication. Intern Med. 2020;59(2):153–61. https://doi.org/10.2169/internalmedicine.2521-18 .

Kakiuchi T, Mizoe A, Yamamoto K, Imamura I, Hashiguchi K, Kawakubo H, et al. Effect of probiotics during vonoprazan-containing triple therapy on gut microbiota in Helicobacter pylori infection: A randomized controlled trial. Helicobacter. 2020;25(3):e12690. https://doi.org/10.1111/hel.12690 .

Kajino M, Hasuoka A, Tarui N, Takagi T. Preparation of pyrrole derivatives as proton pump inhibitors. 2006. WO2006036024A1.

Lu X, Zhang Y, Huo L, Li Z, Zhao Q, Zhou J, et al. A kind of preparation method of vonoprazan fumarate. 2015. CN105085484A.

Ikemoto T, Mizufune H, Nagata T, Sera M, Fukuda N, Yamasaki T. Process for the preparation of pyrrole compound. 2010. WO2010098351A1.

Geng F, Liu Y, Liu X. Method for preparing vonoprazan fumarate. 2015. CN104860923A.

Margot NA, Naik V, VanderVeen L, Anoshchenko O, Singh R, Dvory-Sobol H, et al. Resistance analyses in highly treatment-experienced people with human immunodeficiency virus (HIV) treated with the novel capsid HIV inhibitor lenacapavir. J Infect Dis. 2022;226(11):1985–91. https://doi.org/10.1093/infdis/jiac364 .

Dvory-Sobol H, Shaik N, Callebaut C, Rhee MS. Lenacapavir: A first-in-class HIV-1 capsid inhibitor. Curr Opin HIV AIDS. 2022;17(1):15–21. https://doi.org/10.1097/coh.0000000000000713 .

Zhuang S, Torbett BE. Interactions of HIV-1 capsid with host factors and their implications for developing novel therapeutics. Viruses. 2021;13(3):417. https://doi.org/10.3390/v13030417 .

Margot N, Ram R, Rhee M, Callebaut C. Absence of lenacapavir (GS-6207) phenotypic resistance in HIV gag cleavage site mutants and in isolates with resistance to existing drug classes. Antimicrob Agents Ch. 2021;65(3):e02057-e2120. https://doi.org/10.1128/AAC.02057-20 .

Bester SM, Wei G, Zhao H, Adu-Ampratwum D, Iqbal N, Courouble VV, et al. Structural and mechanistic bases for a potent HIV-1 capsid inhibitor. Science. 2020;370(6514):360–4. https://doi.org/10.1126/science.abb4808 .

Nka AD, Bouba Y, Teto G, Semengue ENJ, Takou DK, Ngueko AMK, et al. Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals. J Antimicrob Chemother. 2022;78(1):272–5. https://doi.org/10.1093/jac/dkac388 .

Bester SM, Adu-Ampratwum D, Annamalai AS, Wei G, Briganti L, Murphy BC, et al. Structural and mechanistic bases of viral resistance to HIV-1 capsid inhibitor lenacapavir. mBio. 2022;13(5):e0180422. https://doi.org/10.1128/mbio.01804-22 .

Allan KM, Batten AL, Brizgys G, Dhar S, Doxsee IJ, Goldberg A, et al. Methods and intermediates for preparation of antiretroviral pyridine derivative useful for treatment of HIV-1 infections. 2019. WO2019035973A1.

Markham A. Daridorexant: First approval. Drugs. 2022;82(5):601–7. https://doi.org/10.1007/s40265-022-01699-y .

Morin AK, Jarvis CI, Lynch AM. Therapeutic options for sleep-maintenance and sleep-onset insomnia. Pharmacotherapy. 2007;27(1):89–110. https://doi.org/10.1592/phco.27.1.89 .

Roecker AJ, Cox CD, Coleman PJ. Orexin receptor antagonists: New therapeutic agents for the treatment of insomnia. J Med Chem. 2016;59(2):504–30. https://doi.org/10.1021/acs.jmedchem.5b00832 .

Onge ES, Phillips B, Rowe C. Daridorexant: a new dual orexin receptor antagonist for insomnia. J Pharm Technol. 2022;38(5):297–303. https://doi.org/10.1177/87551225221112546 .

Roch C, Bergamini G, Steiner MA, Clozel M. Nonclinical pharmacology of daridorexant: A new dual orexin receptor antagonist for the treatment of insomnia. Psychopharmacology. 2021;238(10):2693–708. https://doi.org/10.1007/s00213-021-05954-0 .

Herring WJ, Roth T, Krystal AD, Michelson D. Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications. J Sleep Res. 2019;28(2):e12782. https://doi.org/10.1111/jsr.12782 .

Boss C, Brotschi C, Gude M, Heidmann B, Sifferlen T, Von Raumer M, et al. Crystalline salt form of (S)-(2-(6-chloro-7-methyl-1 h-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone as orexin receptor antagonist. 2015. WO2015083071.

Nohria V, Giller E. Ganaxolone. Neurotherapeutics. 2007;4(1):102–5. https://doi.org/10.1016/j.nurt.2006.11.003 .

Olson HE, Demarest ST, Pestana-Knight EM, Swanson LC, Iqbal S, Lal D, et al. Cyclin-dependent kinase-like 5 deficiency disorder: Clinical review. Pediatr Neurol. 2019;97:18–25. https://doi.org/10.1016/j.pediatrneurol.2019.02.015 .

Vaitkevicius H, Ramsay RE, Swisher CB, Husain AM, Aimetti A, Gasior M. Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial. Epilepsia. 2022;63(9):2381–91. https://doi.org/10.1111/epi.17343 .

Monaghan EP, Navalta LA, Shum L, Ashbrook DW, Lee DA. Initial human experience with ganaxolone, a neuroactive steroid with antiepileptic activity. Epilepsia. 1997;38(9):1026–31. https://doi.org/10.1111/j.1528-1157.1997.tb01486.x .

Reddy DS, Woodward R. Ganaxolone: A prospective overview. Drugs Future. 2004;29(3):227–42. https://doi.org/10.1358/dof.2004.029.03.793135 .

Belelli D, Lambert JJ. Neurosteroids: Endogenous regulators of the GABAA receptor. Nat Rev Neurosci. 2005;6(7):565–75. https://doi.org/10.1038/nrn1703 .

Dichtel LE, Nyer M, Dording C, Fisher LB, Cusin C, Shapero BG, et al. Effects of open-label, adjunctive ganaxolone on persistent depression despite adequate antidepressant treatment in postmenopausal women: A pilot study. J Clin Psychiatry. 2020;81(4):19m12887. https://doi.org/10.4088/JCP.19m12887 .

Wilkinson ST, Sanacora G. A new generation of antidepressants: An update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems. Drug Discov Today. 2019;24(2):606–15. https://doi.org/10.1016/j.drudis.2018.11.007 .

Gonda X, Dome P, Neill JC, Tarazi FI. Novel antidepressant drugs: Beyond monoamine targets. CNS Spectr. 2023;28(1):6–15. https://doi.org/10.1017/s1092852921000791 .

Reddy DS. Preparation of Neurosteroid compounds and use in treating central nervous system disorders. 2019. WO2019209850A1.

Martinez Botella G, Salituro FG, Robichaud AJ, Harrison BL. Preparation of neuroactive steroids, compositions and methods for treating CNS disorders. 2016. WO2016061527A1.

He M-h, Liao Q-j. Synthesis of ganaxalone. Chin J New Drug. 2005;14(8):1025–6.

CAS Google Scholar

Kusaczuk M, Bartoszewicz M, Cechowska-Pasko M. Phenylbutyric Acid: Simple structure-multiple effects. Curr Pharm Des. 2015;21(16):2147–66. https://doi.org/10.2174/1381612821666150105160059 .

Kasumov T, Brunengraber LL, Comte B, Puchowicz MA, Jobbins K, Thomas K, et al. New secondary metabolites of phenylbutyrate in humans and rats. Drug Metab Dispos. 2004;32(1):10–9. https://doi.org/10.1124/dmd.32.1.10 .

Koetsier MJ, Jekel PA, van den Berg MA, Bovenberg RA, Janssen DB. Characterization of a phenylacetate-CoA ligase from Penicillium chrysogenum. Biochem J. 2009;417(2):467–76. https://doi.org/10.1042/bj20081257 .

Albanese A, Ludolph AC, McDermott CJ, Corcia P, Van Damme P, Van den Berg LH, et al. Tauroursodeoxycholic acid in patients with amyotrophic lateral sclerosis: The TUDCA-ALS trial protocol. Front Neurol. 2022;13:1009113. https://doi.org/10.3389/fneur.2022.1009113 .

Vang S, Longley K, Steer CJ, Low WC. The unexpected uses of urso-and tauroursodeoxycholic acid in the treatment of non-liver diseases. Glob Adv Health Med. 2014;3(3):58–69. https://doi.org/10.7453/gahmj.2014.017 .

Ahn TK, Kim KT, Joshi HP, Park KH, Kyung JW, Choi UY, et al. Therapeutic potential of tauroursodeoxycholic acid for the treatment of osteoporosis. Int J Mol Sci. 2020;21(12):4274. https://doi.org/10.3390/ijms21124274 .

Lu Q, Jiang Z, Wang Q, Hu H, Zhao G. The effect of tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation. Ann Hepato. 2021;23:100289. https://doi.org/10.1016/j.aohep.2020.100289 .

Heo YA. Sodium phenylbutyrate and ursodoxicoltaurine: First approval. CNS Drugs. 2022;36(9):1007–13. https://doi.org/10.1007/s40263-022-00945-x .

Mullard A. Amylyx’s ALS therapy secures FDA approval, as regulatory flexibility trumps underwhelming data. Nat Rev Drug Discov. 2022;21(11):786. https://doi.org/10.1038/d41573-022-00171-6 .

Morris J. Amyotrophic lateral sclerosis (ALS) and related motor neuron siseases: An overview. Neurodiagn J. 2015;55(3):180–94. https://doi.org/10.1080/21646821.2015.1075181 .

Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017;3:17071. https://doi.org/10.1038/nrdp.2017.71 .

Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, et al. Amyotrophic lateral sclerosis. Lancet. 2022;400(10360):1363–80. https://doi.org/10.1016/s0140-6736(22)01272-7 .

Meyer T. Amyotrophic lateral sclerosis (ALS)-diagnosis, course of disease and treatment options. Dtsch Med Wochenschr. 2021;146(24/25):1613–8. https://doi.org/10.1055/a-1562-7882 .

Paganoni S, Macklin EA, Hendrix S, Berry JD, Elliott MA, Maiser S, et al. Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis. New Engl J Med. 2020;383(10):919–30. https://doi.org/10.1056/NEJMoa1916945 .

Martinez-Gonzalez L, Martinez A. Emerging clinical investigational drugs for the treatment of amyotrophic lateral sclerosis. Expert Opin Investig Drugs. 2023;32(2):141–60. https://doi.org/10.1080/13543784.2023.2178416 .

Reid JG, Reddy JP, Paul BJ, Hossain SS. Preparation of cholic acid derivatives. 2022. US20220298202A1.

Niculet E, Bobeica C, Stefanopol IA, Pelin AM, Nechifor A, Onisor C, et al. Once-daily abrocitinib for the treatment of moderate-to-severe atopic dermatitis in adults and Adolescents Aged 12 Years and Over: A short review of current clinical perspectives. Ther Clin Risk Manag. 2022;18:399–407. https://doi.org/10.2147/tcrm.S338661 .

Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004;113(5):651–7. https://doi.org/10.1172/jci21060 .

Perche PO, Cook MK, Feldman SR. Abrocitinib: A new FDA-approved drug for moderate-to-severe atopic dermatitis. Ann Pharmacother. 2023;57(1):86–98. https://doi.org/10.1177/10600280221096713 .

Crowley EL, Nezamololama N, Papp K, Gooderham MJ. Abrocitinib for the treatment of atopic dermatitis. Expert Rev Clin Immu. 2020;16(10):955–62. https://doi.org/10.1080/1744666X.2021.1828068 .

De SK. Abrocitinib: First globally approved selective janus kinase-1 inhibitor for the treatment of atopic dermatitis. CurrMedChem. 2023;30(38):4278–82. https://doi.org/10.2174/0929867330666230216123419 .

Simpson EL, Silverberg JI, Nosbaum A, Winthrop KL, Guttman-Yassky E, Hoffmeister KM, et al. Integrated safety analysis of abrocitinib for the treatment of moderate-to-severe atopic dermatitis from the phase II and phase III clinical trial program. Am J Clin Dermatol. 2021;22(5):693–707. https://doi.org/10.1007/s40257-021-00618-3 .

Iznardo H, Roé E, Serra-Baldrich E, Puig L. Efficacy and safety of JAK1 inhibitor abrocitinib in atopic dermatitis. Pharmaceutics. 2023;15(2):385. https://doi.org/10.3390/pharmaceutics15020385 .

Mikhaylov D, Ungar B, Renert-Yuval Y, Guttman-Yassky E. Oral JAK inhibitors for atopic dermatitis. Ann Allergy Asthma Immunol. 2023;130(5):577–92. https://doi.org/10.1016/j.anai.2023.01.020 .

Coffman KJ, Duerr JM, Kaila N, Parikh MD, Reese MR, Samad T, et al. Preparation of pyrrolo[2,3-d]pyrimidine derivatives and their use as Janus kinase inhibitors. 2016. CA2899888A1.

Kumar R, Karmilowicz MJ, Burke D, Burns MP, Clark LA, Connor CG, et al. Biocatalytic reductive amination from discovery to commercial manufacturing applied to abrocitinib JAK1 inhibitor. Nat Catal. 2021;4:775–82.

Kocienski P. Synthesis of abrocitinib Synfacts. 2021;17(6):0606. https://doi.org/10.1055/s-0040-1719731 .

Vazquez ML, Kaila N, Strohbach JW, Trzupek JD, Brown MF, Flanagan ME, et al. Identification of N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A selective JAK1 clinical candidate for the treatment of autoimmune diseases. J Med Chem. 2018;61(3):1130–52. https://doi.org/10.1021/acs.jmedchem.7b01598 .

Connor CG, DeForest JC, Dietrich P, Do NM, Doyle KM, Eisenbeis S, et al. Development of a nitrene-type rearrangement for the commercial route of the JAK1 inhibitor abrocitinib. Org Process Res Dev. 2021;25(3):608–15. https://doi.org/10.1021/acs.oprd.0c00366 .

Lu X, Zhong Z, Zhang X. Crystal forms of sulfonamide compound and preparation method. 2021. WO2021218948A1.

Ghosh AK, Brindisi M, Sarkar A. The Curtius rearrangement: Applications in modern drug discovery and medicinal chemistry. ChemMedChem. 2018;13(22):2351–73. https://doi.org/10.1002/cmdc.201800518 .

Keam SJ. Tapinarof cream 1%: First approval. Drugs. 2022;82(11):1221–8. https://doi.org/10.1007/s40265-022-01748-6 .

Mason AR, Mason J, Cork M, Dooley G, Hancock H. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev. 2013;3:Cd005028. https://doi.org/10.1002/14651858.CD005028.pub3 .

Bissonnette R, Gold LS, Rubenstein DS, Tallman AM, Armstrong A. Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor–modulating agent. J Am Acad Dermatol. 2021;84(4):1059–67. https://doi.org/10.1016/j.jaad.2020.10.085 .

Pecyna P, Wargula J, Murias M, Kucinska M. More than resveratrol: New insights into stilbene-based compounds. Biomolecules. 2020;10(8):1111. https://doi.org/10.3390/biom10081111 .

Furue M, Hashimoto-Hachiya A, Tsuji G. Aryl hydrocarbon receptor in atopic dermatitis and psoriasis. Int J Mol Sci. 2019;20(21):5424. https://doi.org/10.3390/ijms20215424 .

Smith SH, Jayawickreme C, Rickard DJ, Nicodeme E, Bui T, Simmons C, et al. Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans. J Invest Dermatol. 2017;137(10):2110–9. https://doi.org/10.1016/j.jid.2017.05.004 .

Zhang Y. Clean process for preparation of (E)-3,5-dihydroxy-4-isopropyldiphenylethene. 2010. CN101648851A.

Hoy SM. Deucravacitinib: First approval. Drugs. 2022;82(17):1671–9. https://doi.org/10.1007/s40265-022-01796-y .

Chimalakonda A, Burke J, Cheng L, Catlett I, Tagen M, Zhao Q, et al. Selectivity profile of the tyrosine kinase 2 inhibitor deucravacitinib compared with janus kinase 1/2/3 inhibitors. Dermatol Ther (Heidelb). 2021;11(5):1763–76. https://doi.org/10.1007/s13555-021-00596-8 .

Catlett I, Aras U, Liu Y, Bei D, Girgis I, Murthy B, et al. SAT0226 A first-in-human, study of BMS-986165, a selective, potent, allosteric small molecule inhibitor of tyrosine kinase 2. Ann Rheum Dis. 2017;76(2):859. https://doi.org/10.1136/annrheumdis-2017-eular.3809 .

Wrobleski ST, Moslin R, Lin S, Zhang Y, Spergel S, Kempson J, et al. Highly selective inhibition of tyrosine kinase 2 (TYK2) for the treatment of autoimmune diseases: Discovery of the allosteric inhibitor BMS-986165. J Med Chem. 2019;62(20):8973–95. https://doi.org/10.1021/acs.jmedchem.9b00444 .

Roskoski R Jr. Deucravacitinib is an allosteric TYK2 protein kinase inhibitor FDA-approved for the treatment of psoriasis. Pharmacol Res. 2023;189:106642. https://doi.org/10.1016/j.phrs.2022.106642 .

Mease PJ, Deodhar AA, van der Heijde D, Behrens F, Kivitz AJ, Neal J, et al. Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022;81(6):815–22. https://doi.org/10.1136/annrheumdis-2021-221664 .

Chen K, Deerberg J, Lin D, Dummeldinger M, Inankur B, Kolotuchin SV, et al. A process for the preparation of cyclopropanecarboxamidomethoxymethyltriazolylphenylaminomethylpyridazinecarboxamide. 2018. WO2018183649A1.

Matte A, Federti E, Kung C, Kosinski PA, Narayanaswamy R, Russo R, et al. The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model. J Clin Invest. 2021;131(10):e144206. https://doi.org/10.1172/JCI144206 .

Kung C, Hixon J, Kosinski PA, Cianchetta G, Histen G, Chen Y, et al. AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency. Blood. 2017;130(11):1347–56. https://doi.org/10.1182/blood-2016-11-753525 .

Rab MA, Van Oirschot BA, Kosinski PA, Hixon J, Johnson K, Chubukov V, et al. AG-348 (mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and adenosine triphosphate levels over a broad range of PKLR genotypes. Haematologica. 2021;106(1):238–49. https://doi.org/10.3324/haematol.2019.238865 .

Al-Samkari H, van Beers EJ. Mitapivat, a novel pyruvate kinase activator, for the treatment of hereditary hemolytic anemias. Ther Adv Hematol. 2021;12:20406207211066070. https://doi.org/10.1177/20406207211066070 .

van Wijk R, van Solinge WW. The energy-less red blood cell is lost: Erythrocyte enzyme abnormalities of glycolysis. Blood. 2005;106(13):4034–42. https://doi.org/10.1182/blood-2005-04-1622 .

Sizemore JP, Guo L, Mirmehrabi M, Su Y. Preparation of amorphous and crystalline forms of N-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide useful for treatment of pyruvate kinase associated disorders. 2019. WO2019104134A1.

Salituro FG, Saunders JO, Yan S. Preparation of aroylpiperazines and related compounds as pyruvate kinase M2 modulators useful in treatment of cancer. 2010. US20100331307A1.

Lamb YN. Pacritinib: First approval. Drugs. 2022;82(7):831–8. https://doi.org/10.1007/s40265-022-01718-y .

Genthon A, Killian M, Mertz P, Cathebras P, Gimenez De Mestral S, Guyotat D, et al. Myelofibrosis: A review. Rev Med Interne. 2021;42(2):101–9. https://doi.org/10.1016/j.revmed.2020.08.018 .

Hart S, Goh K, Novotny-Diermayr V, Hu C, Hentze H, Tan Y, et al. SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. Leukemia. 2011;25(11):1751–9. https://doi.org/10.1038/leu.2011.148 .

Singer JW, Al-Fayoumi S, Ma H, Komrokji RS, Mesa R, Verstovsek S. Comprehensive kinase profile of pacritinib, a nonmyelosuppressive janus kinase 2 inhibitor. J Exp Pharmacol. 2016;8:11–9. https://doi.org/10.2147/jep.S110702 .

Komrokji RS, Wadleigh M, Seymour JF, Roberts AW, To LB, Zhu HJ, et al. Results of a phase 2 study of pacritinib (SB1518), a novel oral JAK2 inhibitor, in patients with primary, post-polycythemia vera, and post-essential thrombocythemia myelofibrosis. Blood. 2011;118(21):282.

Venugopal S, Mascarenhas J. The odyssey of pacritinib in myelofibrosis. Blood Adv. 2022;6(16):4905–13. https://doi.org/10.1182/bloodadvances.2022007524 .

Singer J, Al-Fayoumi S, Ma H, Komrokji RS, Mesa R, Verstovsek S. Comprehensive kinase profile of pacritinib, a non-myelosuppressive JAK2 kinase inhibitor in phase 3 development in primary and post ET/PV myelofibrosis. Blood. 2014;124(21):1874.

Mascarenhas J. Pacritinib for the treatment of patients with myelofibrosis and thrombocytopenia. Expert Rev Hematol. 2022;15(8):671–84. https://doi.org/10.1080/17474086.2022.2112565 .

Blanchard S, Lee CHA, Nagaraj HKM, Poulsen AS, Eric T, Tan YLE, William AD. Preparation of oxygen linked pyrimidine macrocyclic derivatives as antiproliferative agents. 2007. WO2007058627A1.

William AD, Lee ACH, Blanchard S, Poulsen A, Teo EL, Nagaraj H, et al. Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J Med Chem. 2011;54(13):4638–58. https://doi.org/10.1021/jm200326p .

Fang H, Lu H, Hou X, Yang X. Preparation method of JAK inhibitor pacritinib. 2022. CN114409674A.

Fallah J, Agrawal S, Gittleman H, Fiero MH, Subramaniam S, John C, et al. FDA approval summary: Iutetium Lu 177 vipivotide tetraxetan for patients with metastatic castration-resistant prostate cancer. Clin Cancer Res. 2023;29(9):1651–7. https://doi.org/10.1158/1078-0432.Ccr-22-2875 .

Liu X, Fang GC, Lu H, Shi ZD, Chen ZS, Han CH. Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Drugs Today (Barc). 2023;59(1):37–49. https://doi.org/10.1358/dot.2023.59.1.3476574 .

Tateishi U. Prostate-specific membrane antigen (PSMA)–ligand positron emission tomography and radioligand therapy (RLT) of prostate cancer. Jpn J Clin Oncol. 2020;50(4):349–56. https://doi.org/10.1093/jjco/hyaa004 .

Emmett L, Willowson K, Violet J, Shin J, Blanksby A, Lee J. Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: A review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 2017;64(1):52–60. https://doi.org/10.1002/jmrs.227 .

Czernin J, Calais J. The (177)Lu-PSMA-617 (Pluvicto) supply problem will be solved by competition. J Nucl Med. 2023;64(3):343. https://doi.org/10.2967/jnumed.123.265459 .

Chandran E, Figg WD, Madan R. Lutetium-177-PSMA-617: A vision of the future. Cancer Biol Ther. 2022;23(1):186–90. https://doi.org/10.1080/15384047.2022.2037985 .

Keam SJ. Lutetium Lu 177 vipivotide tetraxetan: First approval. Mol Diagn Ther. 2022;26(4):467–75. https://doi.org/10.1007/s40291-022-00594-2 .

Benesova M, Schafer M, Bauder-Wust U, Afshar-Oromieh A, Kratochwil C, Mier W, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med. 2015;56(6):914–20. https://doi.org/10.2967/jnumed.114.147413 .

Lin KS, Benard F, Kuo HT, Zhang Z. Novel radiometal-binding compounds for diagnosis or treatment of prostate specific membrane antigen-expressing cancer. 2019. WO2019075583A1.

Syed YY. Futibatinib: First approval. Drugs. 2022;82(18):1737–43. https://doi.org/10.1007/s40265-022-01806-z .

Lamarca A, Barriuso J, McNamara MG, Valle JW. Molecular targeted therapies: Ready for “prime time” in biliary tract cancer. J Hepatol. 2020;73(1):170–85. https://doi.org/10.1016/j.jhep.2020.03.007 .

Kalyukina M, Yosaatmadja Y, Middleditch MJ, Patterson AV, Smaill JB, Squire CJ. TAS-120 cancer target binding: defining reactivity and revealing the first fibroblast growth factor receptor 1 (FGFR1) irreversible structure. ChemMedChem. 2019;14(4):494–500. https://doi.org/10.1002/cmdc.201800719 .

Goyal L, Shi L, Liu LY, Fece de la Cruz F, Lennerz JK, Raghavan S, et al. TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion–positive intrahepatic cholangiocarcinomaTAS-120 efficacy in FGFR inhibitor–resistant biliary cancer. Cancer Discov. 2019;9(8):1064–79. https://doi.org/10.1158/2159-8290.CD-19-0182 .

Sootome H, Fujita H, Ito K, Ochiiwa H, Fujioka Y, Ito K, et al. Futibatinib is a novel irreversible FGFR 1–4 inhibitor that shows selective antitumor activity against FGFR-deregulated tumors irreversible FGFR1–4 inhibitor. Cancer Res. 2020;80(22):4986–97. https://doi.org/10.1158/0008-5472.CAN-19-2568 .

Rizzo A, Ricci AD, Brandi G. Futibatinib, an investigational agent for the treatment of intrahepatic cholangiocarcinoma: Evidence to date and future perspectives. Expert Opin Investig Drugs. 2021;30(4):317–24. https://doi.org/10.1080/13543784.2021.1837774 .

Futibatinib (Lytgobi) for cholangiocarcinoma. Med Lett Drugs Ther. 2023;65(1674):e69-e70. https://doi.org/10.58347/tml.2023.1674f .

Kondo M. Method for producing dimethoxybenzene compound. 2020. WO2020096042A1.

Newell LF, Cook RJ. Advances in acute myeloid leukemia. BMJ. 2021;375:n2026. https://doi.org/10.1136/bmj.n2026 .

Olutasidenib (Rezlidhia) for acute myeloid leukemia. Med Lett Drugs Ther. 2023;65(1673):e58-e59. https://doi.org/10.58347/tml.2023.1673e .

Dang L, Jin S, Su SM. IDH mutations in glioma and acute myeloid leukemia. Trends Mol Med. 2010;16(9):387–97. https://doi.org/10.1016/j.molmed.2010.07.002 .

Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010;17(3):225–34. https://doi.org/10.1016/j.ccr.2010.01.020 .

de Nigris F, Ruosi C, Napoli C. Clinical efficiency of epigenetic drugs therapy in bone malignancies. Bone. 2021;143:115605. https://doi.org/10.1016/j.bone.2020.115605 .

Jones RL, Macarulla T, Charlson JA, Van Tine BA, Goyal L, Italiano A, et al. A phase Ib/II study of olutasidenib in patients with relapsed/refractory IDH1 mutant solid tumors: Safety and efficacy as single agent. J Clin Oncol. 2020;38(15):e16643. https://doi.org/10.1200/JCO.2020.38.15_suppl.e16643 .

De La Fuente MI, Colman H, Rosenthal M, Van Tine BA, Levaci D, Walbert T, et al. A phase Ib/II study of olutasidenib in patients with relapsed/refractory IDH1 mutant gliomas: Safety and efficacy as single agent and in combination with azacitidine. J Clin Oncol. 2020;38(15):2505. https://doi.org/10.1200/JCO.2020.38.15_suppl.2505 .

Caravella JA, Lin J, Diebold RB, Campbell AM, Ericsson A, Gustafson G, et al. Structure-based design and identification of FT-2102 (Olutasidenib), a potent mutant-selective IDH1 inhibitor. J Med Chem. 2020;63(4):1612–23. https://doi.org/10.1021/acs.jmedchem.9b01423 .

Dhillon S. Adagrasib: First approval. Drugs. 2023;83(3):275–85. https://doi.org/10.1007/s40265-023-01839-y .

O’Sullivan É, Keogh A, Henderson B, Finn SP, Gray SG, Gately K. Treatment strategies for KRAS-mutated non-small-cell lung cancer. Cancers (Basel). 2023;15(6):1635. https://doi.org/10.3390/cancers15061635 .

Adagrasib (Krazati) for NSCLC. Med Lett Drugs Ther. 2023;65(1668):e17-e18. https://doi.org/10.58347/tml.2023.1668f .

Rodenhuis S, Boerrigter L, Top B, Slebos RJ, Mooi WJ, van’t Veer L, et al. Mutational activation of the K-ras oncogene and the effect of chemotherapy in advanced adenocarcinoma of the lung: A prospective study. J Clin Oncol. 1997;15(1):285–91. https://doi.org/10.1200/jco.1997.15.1.285 .

Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, et al. The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-Mutant cancers in mouse models and patientstherapeutic insight from the KRASG12C inhibitor MRTX849. Cancer Discov. 2020;10(1):54–71. https://doi.org/10.1158/2159-8290 .

Ou SHI, Jänne PA, Leal TA, Rybkin II, Sabari JK, Barve MA, et al. First-in-human phase I/IB dose-finding study of adagrasib (MRTX849) in patients with advanced KRASG12C solid tumors (KRYSTAL-1). J Clin Oncol. 2022;40(23):2530–8. https://doi.org/10.1200/JCO.21.02752 .

Fell JB, Fischer JP, Baer BR, Blake JF, Bouhana K, Briere DM, et al. Identification of the clinical development candidate MRTX849, a covalent KRASG12C inhibitor for the treatment of cancer. J Med Chem. 2020;63(13):6679–93. https://doi.org/10.1021/acs.jmedchem.9b02052 .

Vishwanatha T, Panguluri NR, Sureshbabu VV. Propanephosphonic acid anhydride (T3P®)-A benign reagent for diverse applications inclusive of large-scale synthesis. Synthesis. 2013;45(12):1569–601. https://doi.org/10.1055/s-0033-1338989 .

Keam SJ. Mavacamten: First approval. Drugs. 2022;82(10):1127–35. https://doi.org/10.1007/s40265-022-01758-4 .

Lakdawala N, Saberi S, Day S, Ingles J, Semsarian C, Olivotto I, et al. New York Heart Association functional class and mortality in obstructive hypertrophic cardiomyopathy. J Card Fail. 2022;28(5):S37–8. https://doi.org/10.1016/j.cardfail.2022.03.101 .

Dalo JD, Weisman ND, White CM. Mavacamten, a first-in-class cardiac myosin inhibitor for obstructive hypertrophic cardiomyopathy. Ann Pharmacother. 2023;57(4):489–502. https://doi.org/10.1177/10600280221117812 .

Fukuda N, Granzier H, Ishiwata S, Morimoto S. Editorial: Recent advances on myocardium physiology, volume II. Front Physiol. 2023;14:1170396. https://doi.org/10.3389/fphys.2023.1170396 .

Gollapudi SK, Ma W, Chakravarthy S, Combs AC, Sa N, Langer S, et al. Two classes of myosin inhibitors, para-nitroblebbistatin and mavacamten, stabilize β-cardiac myosin in different structural and functional states. J Mol Biol. 2021;433(23):167295. https://doi.org/10.1016/j.jmb.2021.167295 .

Green EM, Wakimoto H, Anderson RL, Evanchik MJ, Gorham JM, Harrison BC, et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science. 2016;351(6273):617–21. https://doi.org/10.1126/science.aad3456 .

Stern JA, Markova S, Ueda Y, Kim JB, Pascoe PJ, Evanchik MJ, et al. A small molecule inhibitor of sarcomere contractility acutely relieves left ventricular outflow tract obstruction in feline hypertrophic cardiomyopathy. PLoS One. 2016;11(12):e0168407. https://doi.org/10.1371/journal.pone.0168407 .

Kawas RF, Anderson RL, Ingle SRB, Song Y, Sran AS, Rodriguez HM. A small-molecule modulator of cardiac myosin acts on multiple stages of the myosin chemomechanical cycle. J Biol Chem. 2017;292(40):16571–7. https://doi.org/10.1074/jbc.M117.776815 .

Capilupi MJ, Frishman WH. Mavacamten: A novel disease-specific treatment for hypertrophic cardiomyopathy. Cardiol Rev. 2023;31(1):45–51. https://doi.org/10.1097/crd.0000000000000433 .

Oslob J, Anderson R, Aubele D, Evanchik M, Fox JC, Kane B, et al. Preparation of pyrimidinedione compounds for treating hypertrophic cardiomyopathy (HCM) and other cardiac conditions. 2014. WO2014205223A1.

Singal AK, Jalan R. Terlipressin for hepatorenal syndrome: Opportunities and challenges. Lancet Gastroenterol Hepatol. 2023;8(2):104–6. https://doi.org/10.1016/s2468-1253(22)00377-6 .

Habas E, Ibrahim AR, Moursi MO, Shraim BA, Elgamal ME, Elzouki AN. Update on hepatorenal syndrome: Definition, pathogenesis, and management. Arab J Gastroenterol. 2022;23(2):125–33. https://doi.org/10.1016/j.ajg.2022.01.005 .

O’Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet. 2002;359(9313):1209–10. https://doi.org/10.1016/S0140-6736(02)08225-9 .

Zhou X, Tripathi D, Song T, Shao L, Han B, Zhu J, et al. Terlipressin for the treatment of acute variceal bleeding: a systematic review and meta-analysis of randomized controlled trials. Medicine. 2018;97(48):e13437. https://doi.org/10.1097/MD.0000000000013437 .

Liu X, Luo G, Jiang J, Ma T, Lin X, Jiang L, et al. Signaling through hepatocyte vasopressin receptor 1 protects mouse liver from ischemia-reperfusion injury. Oncotarget. 2016;7(43):69276–90. https://doi.org/10.18632/oncotarget.12472 .

Jao YTFN. Refractory torsade de pointes induced by terlipressin (Glypressin). Int J Cardiol. 2016;222:135–40. https://doi.org/10.1016/j.ijcard.2016.07.247 .

Liu ZM, Zhang XY, Chen J, Shen JT, Jiang ZY, Guan XD. Terlipressin protects intestinal epithelial cells against oxygen-glucose deprivation/re-oxygenation injury via the phosphatidylinositol 3-kinase pathway. Exp Ther Med. 2017;14(1):260–6. https://doi.org/10.3892/etm.2017.4502 .

Pesaturo AB, Jennings HR, Voils SA. Terlipressin: Vasopressin analog and novel drug for septic shock. Ann Pharmacother. 2006;40(12):2170–7. https://doi.org/10.1345/aph.1H373 .

Allegretti AS, Subramanian RM, Francoz C, Olson JC, Cárdenas A. Respiratory events with terlipressin and albumin in hepatorenal syndrome: A review and clinical guidance. Liver Int. 2022;42(10):2124–30. https://doi.org/10.1111/liv.15367 .

Leone M, Charvet A, Delmas A, Albanèse J, Martin C, Boyle WA. Terlipressin: A new therapeutic for calcium-channel blockers overdose. J Crit Care. 2005;1(20):114–5. https://doi.org/10.1016/j.jcrc.2004.10.004 .

Chen Y, Mi P, Tao A, Yuan J. Synthesis method for terlipressin. 2020. WO2020107879A1.

Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, et al. Nephrogenic systemic fibrosis: Suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol. 2006;17(9):2359–62. https://doi.org/10.1681/asn.2006060601 .

Sadowski EA, Bennett LK, Chan MR, Wentland AL, Garrett AL, Garrett RW, et al. Nephrogenic systemic fibrosis: Risk factors and incidence estimation. Radiology. 2007;243(1):148–57. https://doi.org/10.1148/radiol.2431062144 .

Daftari Besheli L, Aran S, Shaqdan K, Kay J, Abujudeh H. Current status of nephrogenic systemic fibrosis. Clin Radiol. 2014;69(7):661–8. https://doi.org/10.1016/j.crad.2014.01.003 .

Robic C, Port M, Rousseaux O, Louguet S, Fretellier N, Catoen S, et al. Physicochemical and pharmacokinetic profiles of gadopiclenol: A new macrocyclic gadolinium chelate with high T1 relaxivity. Invest Radiol. 2019;54(8):475–84. https://doi.org/10.1097/RLI.0000000000000563 .

Bendszus M, Roberts D, Kolumban B, Meza JA, Bereczki D, San-Juan D, et al. Dose finding study of gadopiclenol, a new macrocyclic contrast agent, in MRI of central nervous system. Invest Radiol. 2020;55(3):129–37. https://doi.org/10.1097/RLI.0000000000000624 .

Fries P, Massmann A, Robert P, Corot C, Laschke MW, Schneider G, et al. Evaluation of gadopiclenol and P846, 2 high-relaxivity macrocyclic magnetic resonance contrast agents without protein binding, in a rodent model of hepatic metastases: Potential solutions for improved enhancement at ultrahigh field strength. Invest Radiol. 2019;54(9):549–58. https://doi.org/10.1097/rli.0000000000000572 .

Lancelot E, Raynaud JS, Desché P. Current and future MR contrast agents: Seeking a better chemical stability and relaxivity for optimal safety and efficacy. Invest Radiol. 2020;55(9):578–88. https://doi.org/10.1097/rli.0000000000000684 .

Port M. Compounds comprising short aminoalcohol chains and metal complexes for medical imaging. 2007. WO2007042506A1.

Duggan S. Omidenepag isopropyl ophthalmic solution 0.002%: First global approval. Drugs. 2018;78(18):1925–9. https://doi.org/10.1007/s40265-018-1016-1 .

Matsuo M, Matsuoka Y, Tanito M. Efficacy and patient tolerability of omidenepag isopropyl in the treatment of glaucoma and ocular hypertension. Clin Ophthalmol. 2022;16:1261–79. https://doi.org/10.2147/opth.S340386 .

Iwamura R, Tanaka M, Okanari E, Kirihara T, Odani-Kawabata N, Shams N, et al. Identification of a selective, non-prostanoid EP2 receptor agonist for the treatment of glaucoma: omidenepag and its prodrug omidenepag isopropyl. J Med Chem. 2018;61(15):6869–91. https://doi.org/10.1021/acs.jmedchem.8b00808 .

Kirihara T, Taniguchi T, Yamamura K, Iwamura R, Yoneda K, Odani-Kawabata N, et al. Pharmacologic characterization of omidenepag isopropyl, a novel selective EP2 receptor agonist, as an ocular hypotensive agent. Invest Ophthalmol Vis Sci. 2018;59(1):145–53. https://doi.org/10.1167/iovs.17-22745 .

Nakamura N, Honjo M, Yamagishi R, Igarashi N, Sakata R, Aihara M. Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction. Sci Rep. 2021;11(1):16257. https://doi.org/10.1038/s41598-021-95768-z .

Fuwa M, Toris CB, Fan S, Taniguchi T, Ichikawa M, Odani-Kawabata N, et al. Effects of a novel selective EP2 receptor agonist, omidenepag isopropyl, on aqueous humor dynamics in laser-induced ocular hypertensive monkeys. J Ocul Pharmacol Th. 2018;34(7):531–7. https://doi.org/10.1089/jop.2017.0146 .

Aihara M, Lu F, Kawata H, Iwata A, Odani-Kawabata N, Shams NK. Omidenepag isopropyl versus latanoprost in primary open-angle glaucoma and ocular hypertension: The phase 3 AYAME study. Am J Ophthalmol. 2020;220:53–63. https://doi.org/10.1016/j.ajo.2020.06.003 .

Lamorte L, Titolo S, Lemke CT, Goudreau N, Mercier JF, Wardrop E, et al. Discovery of novel small-molecule HIV-1 replication inhibitors that stabilize capsid complexes. Antimicrob Agents Chemother. 2013;57(10):4622–31. https://doi.org/10.1128/AAC.00985-13 .

Imaizumi T, Akaiwa M, Abe T, Nigawara T, Koike T, Satake Y, et al. Discovery and biological evaluation of 1-{2,7-diazaspiro[3.5]nonan-2-yl}prop-2-en-1-one derivatives as covalent inhibitors of KRAS G12C with favorable metabolic stability and anti-tumor activity. Bioorg Med Chem. 2022;71:116949. https://doi.org/10.1016/j.bmc.2022.116949 .

Download references

Acknowledgements

We extend our sincere appreciation for the generous financial support received from the National Natural Science Foundation of China (No. 82103560).

Author information

Authors and affiliations.

College of Chemistry and Chemical Engineering, Zhengzhou Normal University, Zhengzhou, 450044, China

Jing-Yi Zhang

First People’s Hospital of Shangqiu, Henan Province, Shangqiu, 476100, China

Ya-Tao Wang

Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer, Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China

Ya-Tao Wang, Lu Sun & Sai-Qi Wang

Zhongshan Hospital Affiliated to Dalian University, Dalian, 116001, China

College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, 11439, USA

Zhe-Sheng Chen

You can also search for this author in PubMed Google Scholar

Contributions

The conceptualization of the project was initiated by Zhe-Sheng Chen, Jing-Yi Zhang, and Sai-Qi Wang, who also assumed the responsibility of curating and categorizing relevant scholarly resources. Furthermore, Jing-Yi Zhang, Ya-Tao Wang and Lu Sun made significant contributions to the generation of graphical illustrations and actively collaborated in the construction of an all-encompassing tabular framework. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Lu Sun , Sai-Qi Wang or Zhe-Sheng Chen .

Ethics declarations

Ethics approval and consent to participate, consent for publication, competing interests.

The authors declare that they have no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1., rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Zhang, JY., Wang, YT., Sun, L. et al. Synthesis and clinical application of new drugs approved by FDA in 2022. Mol Biomed 4 , 26 (2023). https://doi.org/10.1186/s43556-023-00138-y

Download citation

Received : 11 March 2023

Accepted : 24 July 2023

Published : 04 September 2023

DOI : https://doi.org/10.1186/s43556-023-00138-y

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Clinical applications
Find a journal
Publish with us
Track your research

COMMENTS

How to Write a Thesis Statement
A thesis statement summarizes the central points of your essay. It is a signpost telling the reader what the essay will argue and why. The best thesis statements are: Concise: A good thesis statement is short and sweet—don't use more words than necessary. State your point clearly and directly in one or two sentences.
Thesis
Thesis. Your thesis is the central claim in your essay—your main insight or idea about your source or topic. Your thesis should appear early in an academic essay, followed by a logically constructed argument that supports this central claim. A strong thesis is arguable, which means a thoughtful reader could disagree with it and therefore ...
Academic Guides: Writing a Paper: Thesis Statements
The thesis statement is the brief articulation of your paper's central argument and purpose. You might hear it referred to as simply a "thesis." Every scholarly paper should have a thesis statement, and strong thesis statements are concise, specific, and arguable. Concise means the thesis is short: perhaps one or two sentences for a shorter paper.
What Is a Thesis?
A thesis statement is a very common component of an essay, particularly in the humanities. It usually comprises 1 or 2 sentences in the introduction of your essay, and should clearly and concisely summarize the central points of your academic essay. A thesis is a long-form piece of academic writing, often taking more than a full semester to ...
Thesis/Central Idea
A thesis statement is a sentence that expresses the central idea of an essay. It's a good idea to decide the topic sentence of a paragraph after writing the working version of an essay's thesis. A topic sentence explains one aspect or point in the thesis and, therefore, should always be more specific and limited than a thesis.
Thesis Statements
A thesis statement: tells the reader how you will interpret the significance of the subject matter under discussion. is a road map for the paper; in other words, it tells the reader what to expect from the rest of the paper. directly answers the question asked of you. A thesis is an interpretation of a question or subject, not the subject itself.
How to Write a Thesis Statement With Examples
A thesis statement provides the foundation for your entire research paper or essay. This statement is the central assertion that you want to express in your essay. A successful thesis statement is one that is made up of one or two sentences clearly laying out your central idea and expressing an informed, reasoned answer to your research question.
What is a thesis
While a thesis identifies and provides an overarching argument, the key to clearly communicating the central point of that argument lies in writing a strong thesis statement. What is a thesis statement? A strong thesis statement (aka thesis sentence) is a concise summary of the main argument or claim of the paper.
PDF Developing a Central Claim
Central Claim What is a thesis? A thesis is the central claim or main argument of an essay. Because it provides a unifying theme for the rest of the essay, it typically appears early on—in shorter papers, most often within the first paragraph or two. The thesis should be analytic or interpretive rather than merely descriptive or factual.
Developing a Thesis Statement
A thesis statement . . . Makes an argumentative assertion about a topic; it states the conclusions that you have reached about your topic. Makes a promise to the reader about the scope, purpose, and direction of your paper. Is focused and specific enough to be "proven" within the boundaries of your paper. Is generally located near the end ...
The Writing Center
A thesis statement is: The statement of the author's position on a topic or subject. Clear, concise, and goes beyond fact or observation to become an idea that needs to be supported (arguable). Often a statement of tension, where the author refutes or complicates an existing assumption or claim (counterargument).
Developing A Thesis
A good thesis has two parts. It should tell what you plan to argue, and it should "telegraph" how you plan to argue—that is, what particular support for your claim is going where in your essay. Steps in Constructing a Thesis. First, analyze your primary sources. Look for tension, interest, ambiguity, controversy, and/or complication.
Thesis Statements
A thesis is the main point or argument of an information source. (Many, but not all, writing assignments, require a thesis.) Thesis are often answer your research question. Note that it does not have to be the only answer to your research question, a strong thesis question gives a reasonable answer. Below are some characteristics of a strong ...
Thesis Statement
The thesis is usually considered the most important sentence of your essay because it outlines the central purpose of your essay in one place. A good thesis will link the subject of an essay with a controlling idea. Consider, for example, the following thesis: People in the past spent a great deal of effort protecting themselves from witches.
4.3: What is a Thesis Statement?
A thesis is the main idea of an essay. It communicates the essay's purpose with clear and concise wording and indicates the direction and scope of the essay. It should not just be a statement of fact nor should it be an announcement of your intentions. It should be an idea, an opinion of yours that needs to be explored, expanded, and ...
How To Use "Central Thesis" In A Sentence: Diving Deeper
A central thesis refers to the main argument or central idea of a piece of writing, whether it is an essay, research paper, or even a speech. It serves as the backbone of the entire work, providing a clear focus and guiding the reader or audience through the author's perspective or position on a particular topic.
What Is a Thesis?
A thesis statement is a very common component of an essay, particularly in the humanities. It usually comprises 1 or 2 sentences in the introduction of your essay, and should clearly and concisely summarise the central points of your academic essay. A thesis is a long-form piece of academic writing, often taking more than a full semester to ...
Evolving a Central Claim: Example 1
Evolving a Central Claim: Example 1. Your central claim (also called a thesis) lies at the heart of your argument. As a contestable and weighty statement, it anchors your essay, encapsulating the most important idea that you will unpack, unveil, and support in your writing. Claims don't blossom fully formed from the phenomenon under ...
PDF Thesis
Thesis Your thesis is the central claim in your essay—your main insight or idea about your source or topic. Your thesis should appear early in an academic essay, followed by a logically constructed argument that supports this central claim. A strong thesis is arguable, which means a thoughtful reader could disagree with it and therefore needs
What Is A Central Thesis
For expository writing, our writers investigate a given idea, evaluate its various evidence, set forth interesting arguments by expounding on the idea, and that too concisely and clearly. Our online essay writing service has the eligibility to write marvelous expository essays for you. View Sample. Liberal Arts and Humanities.
PDF Developing a Central Claim
A thesis is the central claim or main argument of an essay. Because it provides a unifying theme for the rest of the essay, it typically appears early on—in shorter papers, most often within the first paragraph or two. The thesis should be analytic or interpretive rather than merely descriptive or factual. Constructing an original and clear ...
Synthesis and clinical application of new drugs approved by ...
The pharmaceutical industry had a glorious year in 2022, with a total of 37 new drugs including 20 new chemical entities (NCEs) and 17 new biological entities (NBEs) approved by the Food and Drug Administration (FDA). These drugs are mainly concentrated in oncology, central nervous system, antiinfection, hematology, cardiomyopathy, dermatology, digestive system, ophthalmology, MRI enhancer and ...

Writing a Paper: Thesis Statements

Being Specific

Making a Unique Argument

Creating a Debate

Choosing the Right Words

Leaving Room for Discussion

Thesis Mad Libs

Words to Avoid and to Embrace

Related Resources

Walden Resources

Centers and Offices

Student Resources

Have a language expert improve your writing

What Is a Thesis? | Ultimate Guide & Examples

Thesis template

Instantly correct all language mistakes in your text

Table of contents

The only proofreading tool specialized in correcting academic writing - try for free!

Thesis examples

Receive feedback on language, structure, and formatting

Theoretical framework

Cite this Scribbr article

Is this article helpful?

Tegan George

Thesis Statements

Introduction

What is a thesis statement?

How do I create a thesis?

How do I know if my thesis is strong?

Works consulted

How to Write a Solid Thesis Statement

Key Takeaways: Writing a Thesis Statement

Expository Essay Thesis Statement Examples

Types of Thesis Statements

Argument Thesis Statement Examples

Analytical Essay Thesis Statement Examples

What is a thesis | A Complete Guide with Examples

Table of Contents

What is a thesis?

What is a thesis statement?

Different types of thesis statements

Argumentative (or Persuasive) thesis statement

Analytical thesis statement

Expository (or Descriptive) thesis statement

Cause and effect thesis statement

Compare and contrast thesis statement

What is the difference between a thesis and a thesis statement?

15 components of a thesis structure

Acknowledgments

Table of contents

List of figures and tables

Introduction

Literature review section

Methodology

Results (or Findings)

Practical implications (Recommendation) section

References (or Bibliography)

Glossary (optional)

Thesis examples

Checklist for your thesis evaluation

Preparing your thesis defense

Dissertation vs. Thesis

Wrapping up

Frequently Asked Questions

You might also like

AI for Meta Analysis — A Comprehensive Guide

Cybersecurity in Higher Education: Safeguarding Students and Faculty Data

How To Write An Argumentative Essay

What is a thesis statement?

Identify a topic

Consider what your assignment asks you to do

Sample assignment 1

Sample assignment 2

Developing a Thesis Statement–Additional information

Derive a main point from topic

Look for patterns in your evidence

Purpose statement

Derive purpose statement from topic

Compose a draft thesis statement

Question-to-Assertion