异柠檬酸脱氢酶抑制剂研究进展  

Research progress of isocitrate dehydrogenase inhibitors

作　　者：王环玉 赵烨[1] 刘相奎[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室,上海201203

出　　处：《中国新药杂志》2017年第11期1272-1278,共7页Chinese Journal of New Drugs

摘　　要：异柠檬酸脱氢酶(IDH)可以催化异柠檬酸转化为α-酮戊二酸(α-KG),突变IDH则会将α-KG转化为致瘤代谢物D-2-羟戊二酸(D-2HG),同时导致DNA或组蛋白过甲基化。IDH抑制剂能够通过抑制作用使D-2HG减少,诱导组蛋白去甲基化,从而抑制肿瘤发展。本文对现有IDH抑制剂的结构、作用机制、临床研究进行全面综述。Isocitrate dehydrogenase （IDH） catalyzes the conversion of isocitrate to α-ketoglutarate （α-KG）. However, mutant IDH can convert α-KG to the oncometabolite D-2-hydroxyglutarate （D-2HG） , leading to DNA or histone hypermethylation. IDH inhibitors can decrease the level of D-2HG, induce histone demethylation, and finally inhibit tumor development. In this paper, the structure, mechanism, and clinical trials of IDH inhibitors were reviewed in the general.

关 键 词：突变异柠檬酸脱氢酶(mIDH) D-2-羟戊二酸(D-2HG) 过甲基化 IDH抑制剂 

分 类 号：R979[医药卫生—药品]