异柠檬酸脱氢酶抑制剂研究进展

Research progress of isocitrate dehydrogenase inhibitors

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.