GSK-3抑制剂研究进展  

Studies of Glycogen Synthase Kinase-3 Inhibitors

作　　者：张娜[1] 蒋勇军[2] 俞庆森[1] 邹建卫[2] 

机构地区：[1]浙江大学化学系,杭州310027 [2]浙江大学宁波理工学院分子设计与营养工程市重点实验室,宁波315104

出　　处：《化学进展》2007年第4期614-623,共10页Progress in Chemistry

基　　金：浙江省自然基金(Y405516);宁波市自然基金项目(2006A610042)资助

摘　　要：糖原合成酶激酶-3(glycogen synthase kinase-3,GSK-3)是一个多功能的丝氨酸/苏氨酸蛋白激酶,不仅参与肝糖代谢过程,而且还参与Wnt和Hedgehog信号通路,通过磷酸化多种底物蛋白来调节细胞的生理过程。GSK-3抑制剂作为目前备受关注的小分子抑制剂,对治疗神经退化性疾病、癌症、Ⅱ型糖尿病具有潜在的疗效。本文针对已开发出的GSK-3抑制剂,对其结构、与蛋白的作用模式以及构效关系进行阐述,为进一步设计合理的药物先导化合物和特异性小分子化学探针提供有益的启示。Glycogen synthase kinase-3 （GSK-3）, a muhifunctional serine-threonine kinase, has played an important role in glycogen metabolism and is known to occupy a central stage in many cellular physiological events by phosphorylation of muhifold substrate proteins, including Wnt and Hedgehog signal transduction pathways. Small molecular inhibitors of GSK-3, as new promising drugs for the treatment of neuro-degenerative diseases, cancer and type 1I diabetes, are getting more and more attentions. Information gained from their structures, binding modes and structureactivity relationships provides some clues for the future optimization of drug lead-compounds and selective chemical probes.

关 键 词：GSK-3抑制剂 构效关系 选择性 药物设计 

分 类 号：Q559[生物学—生物化学] R914.2[医药卫生—药物化学]