Professor Yimin Cui's team from the Department of Pharmaceutical Affairs Management and Clinical Pharmacy published a blockbuster review in the journal STTT, a sub-journal of Nature: Targeting Integrin Pathways: From Signaling Pathways to Therapeutic Strategies

On January 2, 2023, the team of Professor Cui Yimin from the Department of Pharmaceutical Affairs Management and Clinical Pharmacy of Peking University School of Pharmacy presented in the Signal Transduction and Targeted sub-journal Nature The journal Therapy (STTT, Q1, IF=38.
1) published an online article titled "Targeting integrin pathways: Mechanisms and advances in therapy", which systematically reviews the historical process of integrin research, introduces integrin and its mediated downstream signal transduction, and the important role played by integrins in the development and development of multiple diseases, and deeply analyzes the development trend of integrin-targeted drugs and the focus of
future clinical research, basic research and translational research.

In 2022, the Lasker Prize in Medicine was awarded to Richard Hynes, Erkki Ruoslahti, and Timothy Springer for their pioneering research in the discovery of integrins.
This has once again brought attention to
the field of integrins.
Integrin research originated in the 80s of last century, and after more than 40 years of efforts, integrin related research has made great progress
.
Integrin plays an important role in cancer, fibrotic diseases, cardiovascular diseases, autoimmune diseases and other diseases, and about 90 drugs or imaging agents targeting integrin have entered clinical research
.
Due to the complexity of the integrin action characteristics and regulatory mechanism, the development process of integrin-targeted drugs is not ideal
.
To date, only 7 integrin-targeted drugs have been successfully marketed
.
An important takeaway from past targeted integrin drug development is that the success of integrin-drug development relies on a deep understanding of integrin regulatory mechanisms and unmet clinical needs
.
Therefore, this review reviews more than 40 years of R&D history of integrins and their key inhibitors, provides a systematic and comprehensive review of all integrin family members and integratin-mediated downstream signal transduction, and analyzes the latest advances
in targeted integrin therapies from laboratory research to clinical development.
In addition, the R&D trend of targeted integrin therapy was further discussed, and an in-depth analysis
was conducted on how to improve the success rate of clinical trials of targeted integrin therapy, as well as conducting clinical research, basic research and translational research.

Figure 1 Integrin research and its landmark drug and inhibitor development milestones over the past four decades

In 2022, a series of major breakthroughs in the field of targeted integrin therapy research have been achieved, including the success of the phase III clinical trial of 99mTc-3PRGD2 imaging agent, PMDA in Japan Carotegrast, the first orally targeted integrin, and the oral integrin-alphavβ6/αvβ1 antagonist PLN-74809 IIa in patients with idiopathic pulmonary fibrosis were approved Phase II clinical trials have yielded positive safety and efficacy data, among other things, and these studies highlight the significant market
development of targeted integrin therapies.

Figure 2 Integrin-related signaling pathways

This review introduces the structure, classification, and signal transduction of integrins, highlights the functions of integrins in the progression of different diseases such as tumors, fibrotic diseases, cardiovascular diseases, infectious diseases, and autoimmune diseases, and summarizes the latest clinical research progress in targeted integrin therapy, including small molecules, antibodies, peptides, antibody conjugates (ADCs), and peptide conjugates (PDCs).
), chimeric antigen receptor T cell (CAR-T) immunotherapy and imaging agent.

Finally, the review discusses the future development direction of basic integrin research, clinical research and translational research, and provides new ideas
for the development of targeted integrin drugs and imaging agents.

Associate Professor Pang Xiaocong, Assistant Researcher Qiu Zhiwei, Department of Pharmacy, Peking University First Hospital, and Dr.
He Xu and Dr.
Zhang Hanxu of our department are the joint first authors
of the article.
Professor Cui Yimin and Professor Xiang Qian of the Department of Pharmaceutical Affairs Management and Clinical Pharmacy are co-corresponding authors
.
Professor Cui Yimin's team is committed to the research and development of innovative drugs and early clinical evaluation in the field of panvascular diseases, and the targeted integrin therapy independently developed by the team has also made important progress and is promoting translation
.
The research results have been supported and funded
by a number of scientific funds such as the National Natural Science Foundation of China, the National Key Research and Development Program, and the Clinical Research Business Funds of the Central High-level Hospital.

About the corresponding author:

Yimin Cui, Doctor of Clinical Pharmacology (M.
D&Ph.
D), Professor, Chief Pharmacist, Doctoral Supervisor
.
He is currently the director of the Institute of Clinical Pharmacology of Peking University, the director of the Clinical Trial Center and the director of the Department of Pharmacy of Peking University First Hospital, and the deputy director
of the Department of Pharmaceutical Affairs Management and Clinical Pharmacy of Peking University School of Pharmacy.
Professor Cui Yimin has long been engaged in early clinical research of innovative drugs and national new drug review technology transformation research, and is committed to the establishment
of pharmaceutical services and innovation transformation system throughout the life cycle.
As the chief expert, Professor Cui Yimin has presided over more than ten national, provincial and ministerial projects
.
It has published at a high level in international authoritative journals such as Nature Reviews, Drug Discovery, JAMA Oncology, JACC, APS-B, etc He has nearly 300 papers, participated in many books on clinical pharmacy and clinical pharmacology as chief editor or associate editor, and served as the executive editor of the Chinese Journal of Clinical Pharmacology, Journal of Clinical Pharmacy and Therapeutics (JCPT).
Editor-in-chief
.
He has won the first prize of the Science and Technology Award of the Chinese Pharmaceutical Association, the Wu Jieping Paul Janssen Medical Pharmacy Award, the WuXi AppTec Life Chemistry Research Award Scholar Award, the China Pharmaceutical Development Award Outstanding Achievement Award for Innovative Drugs, the innovation team leader of the "Innovative Talent Promotion Program" of the Ministry of Science and Technology, and the Peking University Teaching Excellence Award.

Xiang Qian, professor, doctoral supervisor
.
Ph.
D.
from Peking University, visiting scholar
at Johns Hopkins University.
He served as a director of the Chinese Pharmacological Society, the secretary-general of the Clinical Pharmacology Professional Committee of the Chinese Pharmacological Society and other social positions
.
He has long been engaged in clinical pharmacology of antithrombotic and antitumor professional clinical pharmacology, and engaged in clinical research
such as pharmacodynamic evaluation, individualized treatment, and evaluation of new drugs and new biomarkers.
He has undertaken 4 projects of the National Natural Science Foundation of China and 1 sub-project of major new drug creation projects
.
He has published more than 100 papers in JACC, Pharmacol Ther, Stroke, and AJPS In high-level domestic and foreign journals, he has published a number of representative papers as the first author or responsible author, and more than ten invention patents and software copyrights
.
The project won the first prize of the Science and Technology Progress Award of the Chinese Pharmaceutical Association, the second prize of the Science and Technology Progress Award of the Chinese Pharmaceutical Association, and the third prize of the Huaxia Medical Award
.

About the first author:

Pang Xiaocong, Ph.
D.
in Pharmacology, Associate Researcher, Master Supervisor
.
Engaged in the development and evaluation of innovative drugs derived from clinical needs
.
In 2019, he was selected into the Young Talents Recruitment Project of China Association for Science and Technology and Beijing Association for Science and Technology, and served as a young scholar member of the International Union of Basic and Clinical Pharmacology (IUPHAR), the secretary-general of the Youth Committee of the Clinical Pharmacology Professional Committee of the Chinese Pharmacological Society, a director of the Beijing Pharmacological Society, and the Chinese Journal of Clinical Pharmacology Editorial Board Member, etc
.
At present, he is the first author or corresponding author in the international authoritative journals Signal Transduction and Targeted Therapy, JAMA Oncology, and Pharmacological Research He has published more than 20 high-level papers, authorized 2 domestic patents and 1 international PCT patent
.
At present, he has presided over more than 10 national, provincial and academy-level scientific research projects, and won the first prize of the 3rd Capital Medical Innovation and Achievement Transformation Competition
.

Contributed by the Department of Pharmaceutical Affairs Management and Clinical Pharmacy