碳酸酐酶ix小分子抑制剂研析进展.pdfVIP

药学学报 Acta Pharmaceutica Sinica 20 13, 48 ( 11): 1637 1643 ·1637 · 酸酐酶IX 小分子抑制剂的研究进展 1, 2 1, 2 1, 2 1, 2* 佳 , 李凤然 , 刘 洋 , 程卯生 (沈阳 科大学 1. 基于靶点的药物设计与研究教育部重点实验室, 2. 制 工程学院, 辽宁 沈阳 110016) 摘要: 碳酸酐酶IX (CA IX) 是一个肿瘤相关蛋白, 由于其在多种肿瘤组织中高度表达而在正常组织中几乎 不表达, 近年来成为一个潜在的抗癌靶点。寻找能够选择性抑制CA IX 的小分子抑制剂将成为未来的焦点。本 文对其在肿瘤生理活动中的作用、三维晶体结构的特征及小分子抑制剂研究进展进行综述。 关键词: 碳酸酐酶IX; 抑制剂; 缺氧; 抗肿瘤 中图分类号: R9 16 文献标识码: A 文章编号: 0513-4870 (20 13) 11-1637-07 Progress in the study of carbonic anhydrase inhibitors as potential anticancer drugs GUO Jia1, 2 , LI Feng-ran 1, 2 , LIU Yang1, 2, CHENG Mao-sheng1, 2* (1. Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education) ; 2. School of Pharmaceutical Engineering, Sheny ang Pharmaceutical University, Sheny ang 110016, China ) Abstract : Carbonic anhydrase IX (CA IX) is a tumor associated protein which is able to be a potent anticancer target, since it is highly expressed in a multitude of carcinomas, while it is present in a limited number of normal tissues. This review focuses on its role in tumor physiology, the most recent three dimensional structure features of this enzyme which has recently been elucidated. In addition, we present recent advances in the development of small inhibitors able to target CA IX for therapeutic applications. Key words: carbonic anhydrase IX; inhibitor; hypoxic; anti-tumor 碳酸酐酶 (carbonic anhydrase, CA) 是一类普 一个令人瞩目的新型抗肿瘤策略。 遍存在于生物体内的含锌金属酶, 催化二氧化碳的 1 碳酸酐酶IX 在肿瘤生理中的作用 可逆水合反应, 维持细胞内外pH 的平衡