Recent advances of small-molecule c-Src inhibitors for potential therapeutic utilities

Xia-Wen Dang; Ji-Long Duan; Emily Ye; Nian-Dong Mao; RenRen Bai; Xinglu Zhou; Xiang-Yang Ye

doi:10.1016/j.bioorg.2023.106934

Recent advances of small-molecule c-Src inhibitors for potential therapeutic utilities

Bioorg Chem. 2023 Oct 23:142:106934. doi: 10.1016/j.bioorg.2023.106934. Online ahead of print.

Authors

Xia-Wen Dang¹, Ji-Long Duan¹, Emily Ye², Nian-Dong Mao³, RenRen Bai⁴, Xinglu Zhou⁵, Xiang-Yang Ye⁶

Affiliations

¹ School of Pharmacy, Key Laboratory of Elemene Class Anticancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
² Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
³ College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
⁴ School of Pharmacy, Key Laboratory of Elemene Class Anticancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China. Electronic address: [email protected].
⁵ Drug Discovery, Hangzhou HealZen Therapeutics Co., Ltd., Hangzhou, Zhejiang 310018, China. Electronic address: [email protected].
⁶ School of Pharmacy, Key Laboratory of Elemene Class Anticancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China. Electronic address: [email protected].

PMID: 39492169
DOI: 10.1016/j.bioorg.2023.106934

Abstract

Proto-oncogene tyrosine-protein kinase Src, also known as c-Src, belongs to the family of non-receptor tyrosine protein kinases (TKs) called Src kinases. It plays a crucial role in cell division, motility, adhesion, and survival in both normal cells and cancer cells by activating various signaling pathways mediated by multiple cytokines. Additionally, c-Src kinase has been implicated in osteoclasts and bone loss diseases mediated by inflammation and osteoporosis. In recent years, remarkable advancements have been achieved in the development of c-Src inhibitors, with several candidates progressing to the clinical stage. This review focuses on the research progress in several areas, including the mechanism of action, drug discovery, combination therapy, and clinical research. By presenting this information, we aim to provide researchers with convenient access to valuable insights and inspire new ideas to expedite future drug discovery programs.

Keywords: C-Src; Small-molecule inhibitors; Therapeutic utilities; Tyrosine protein kinase (TKs).

Publication types

Review