补体因子B小分子抑制剂研究进展  

Research progress in small molecule inhibitors of complement factor B

作　　者：文帅 赵耀 王燕 李幸 牟伊 姜正羽 WEN Shuai;ZHAO Yao;WANG Yan;LI Xing;MOU Yi;JIANG Zheng-yu(College of Pharmacy and Chemistry&Chemical Engineering,Taizhou University,Taizhou 225300,China;Jiangsu Key Laboratory of Drug Design and Optimization,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]泰州学院医药与化学化工学院,江苏泰州225300 [2]中国药科大学药学院,江苏省药物分子设计与成药性优化重点实验室,江苏南京210009

出　　处：《药学学报》2025年第1期37-47,共11页Acta Pharmaceutica Sinica

基　　金：江苏省高校自然科学基金资助项目(21KJB350008);泰州市社会发展项目(TN202135)。

摘　　要：补体系统的旁路途径是多种疾病发病的关键因素,包括阵发性睡眠性血红蛋白尿、非典型溶血性尿毒症综合征、C3肾小球病、年龄相关性黄斑变性等。补体因子B(complement factor B,CFB)是一种胰蛋白酶样丝氨酸蛋白,以潜伏形式在人体血液中循环。其作为补体旁路途径的关键节点,是治疗补体系统介导疾病的重要靶点。随着伊普可泮(iptacopan)的成功上市,使得CFB小分子抑制剂成为目前的研究热点,国内外多家制药公司都在积极研发CFB小分子抑制剂。本文主要就近年来CFB小分子抑制剂的研究进展做了系统总结,按照结构类型和设计思路对代表化合物及其活性进行了介绍,从而为后续CFB小分子抑制剂的研究提供借鉴和思路。The alternative pathway(AP)of the complement system is a key contributor to the pathogenesis of several diseases including paroxysmal nocturnal hemoglobinuria(PNH),atypical hemolytic uremic syndrome(aHUS),C3 glomerular disease(C3G)and age-related macular degeneration(AMD).Complement factor B(CFB)is a trypsin-like serine protein that circulates in the human bloodstream in a latent form.As a key node of the alternative pathway,it is an important target for the treatment of diseases mediated by the complement system.With the successful launch of iptacopan,the CFB small molecule inhibitors has become a current research hotspot,a number of domestic and foreign pharmaceutical companies are actively developing CFB small molecule inhibitors.In this paper,the research progress of CFB small molecule inhibitors in recent years is systematically summarized,the representative compounds and their activities are introduced according to structural types and design ideas,so as to provide reference and ideas for the subsequent research on CFB small molecule inhibitors.

关 键 词：补体系统 旁路途径 补体因子B 补体因子B小分子抑制剂 

分 类 号：R914[医药卫生—药物化学]