摘要
谷胱甘肽巯基转移酶π(GSTπ)是一种II相代谢酶,在大多数肿瘤细胞中有较高水平的表达。GSTπ可以催化体内外来源的亲电物质和谷胱甘肽(GSH)结合,保护细胞免受损害。但大多数化疗药物也是其作用的对象,GSTπ催化化疗药物和GSH结合,然后以复合物形式被多药耐药相关蛋白排出体外,产生肿瘤耐药作用;另一方面,GSTπ和c-jun N-末端激酶结合,阻断有丝分裂原活化蛋白激酶途径,阻碍肿瘤细胞凋亡。因此,GSTπ不仅是研发抗肿瘤药物的靶点,更是研究新型抗耐药作用肿瘤治疗药物的重要靶点。结合本课题组的研究工作,本文系统总结了近些年靶向GSTπ的抗肿瘤药物研究进展,主要为GSTπ抑制剂和作用于GSTπ的前药等相关研究提供一些新思路。
Glutathione S-transferase（GSTπ）, one of the phase II detoxification enzymes, is usually over- expressed in many human tumors. It displays a key role in protecting cells through catalyzing the conjugation of glutathione（GSH） with a broad range of electrophilic substrates including chemotherapeutic agents. As the above conjugates can be effluxed from cells easily, the efficacy of various chemotherapeutic agents is reduced. Recent studies suggest that GSTπ also plays an important role in inhibiting apoptosis through blocking the JNK signaling pathway. In this way, GSTπ protects cells from apoptosis. Therefore, GSTπ has become an attractive target against cancers, especially for drug-resistant tumors. A great deal of effort has been devoted to the discovery of GSTπ inhibitors and prodrugs over the last decade. In connection with authors＇ current research, we provide a review on studies on progress of GSTπ inhibitors and prodrugs along with the future strategies.
出处
《药学学报》
CAS
CSCD
北大核心
2016年第2期241-247,共7页
Acta Pharmaceutica Sinica
关键词
谷胱甘肽-S-转移酶
抑制剂
抗肿瘤
前药
耐药
glutathione S-transferase π
inhibitor
anticancer
prodrug
drug-resistant
