选择性碳酸酐酶Ⅸ抑制剂的研究进展  

Recent advances of novel selective inhibitors targeting carbonic anhydrase Ⅸ

作　　者：张作鹏[1] 闫海宁 张淼[1] 程卯生[1] 刘洋[1] ZHANG Zuo-peng;YAN Hai-ning;ZHANG Miao;CHENG Mao-sheng;LIU Yang(Key Laboratory of Structure-Based Drug Design & Discovery (Shenyang Pharmaceutical University),Ministry of Education,Shenyang 110016,China)

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室

出　　处：《中国药物化学杂志》2019年第2期135-146,共12页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(81473087);辽宁省自然科学基金重点项目(20170540849);辽宁省高等学校创新人才支持计划项目(LR2017043)

摘　　要：碳酸酐酶(carbonic anhydrases,CAs)是一类广泛分布于生物体内的金属酶,催化生物体内二氧化碳和碳酸氢根离子的相互转化。CAK在正常组织中几乎不表达而在许多实体瘤中过度表达,促进肿瘤细胞的存活及转移性扩散,因此被确定为肿瘤相关蛋白。自1992年CAK的结构被确定以来,CAK抑制剂发展为药物化学领域的研究热点之一,四大类经典的碳酸酐酶抑制剂(CAIs)以及一些新型选择性CAIs不断被发现,部分化合物进人了临床研究阶段。本文对近5年CAK选择性抑制剂的研究进展进行综述。Carbonic anhydrases(CAs),the prevalent metalloenzymes in all life kingdoms,catalyze the efficient interconversion between CO2 and bicarbonate.Carbonic anhydrase IX is a tumor-associated protein,since it scarcely presents in normal tissues,but highly overexpresses in many solid tumors,where it actively contributes to survival and metastatic spread of tumor cells.Since the structure of CAIX was identified in 1992,its inhibitors have always been the research focus in the field of medicinal chemistry.Along with the further research,researchers have developed four classes of classical carbonic anhydrase inhibitors(CAIs)and some novel selective CAIs,among which one has been studied in clinical trials.The research progresses on selective CAIs during the recent five years were summarized in this review.

关 键 词：碳酸酐酶IX 肿瘤相关蛋白 选择性碳酸酐酶抑制剂 

分 类 号：R914[医药卫生—药物化学]