Directly targeting BAX for drug discovery:Therapeutic opportunities and challenges
作者机构：Key Laboratory of Structure-Based Drugs Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China China Resources Sanjiu Medical&Pharmaceutical Co.Ltd.Shenzhen 518000China
出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)
年 卷 期：2024年第14卷第6期
页 面：2378-2401页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：supported by the National Natural Science Foundation of China(Grant No.82173687,82204218) Liaoning Revitalization Talents Program(XLYC1902089,China) Natural Science Foundation of Liaoning Province(2020-BS-155,China) General Scientific Research Projects of Department of Education in Liaoning Province(LJKQZ2021032,LJKZ0930,China) Excellent Youth Talent Support Program of Shenyang Pharmaceutical University(YQ202304,China)
主 题：Apoptosis Pro-apoptotic protein BAX Dynamic conformational activation Small-molecule apoptosis modulators
摘 要：For over two decades,the development of B-cell lymphoma-2(Bcl-2)family therapeutics has primarily focused on anti-apoptotic proteins,resulting in the first-in-class drugs called BH3 mimetics,especially for Bcl-2 inhibitor *** pro-apoptotic protein Bcl-2-associated X protein(BAX)plays a crucial role as the executioner protein of the mitochondrial regulated cell death,contributing to organismal development,tissue homeostasis,and *** dysregulation of BAX is closely associated with the onset and progression of diseases characterized by pathologic cell survival or death,such as cancer,neurodegeneration,and heart *** addition to conducting thorough investigations into the physiological modulation of BAX,research on the regulatory mechanisms of small molecules identified through biochemical screening approaches has prompted the identification of functional and potentially druggable binding sites on BAX,as well as diverse all-molecule BAX *** review presents recent advancements in elucidating the physiological and pharmacological modulation of BAX and in identifying potentially druggable binding sites on ***,it highlights the structural and mechanistic insights into small-molecule modulators targeting diverse binding surfaces or conformations of BAX,offering a promising avenue for developing next-generation apoptosis modulators to treat a wide range of diseases associated with dysregulated cell death by directly targeting BAX.
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