摘要
异柠檬酸脱氢酶(IDH)是人体代谢过程中重要的酶,参与三羧酸循环,催化异柠檬酸转化为α-酮戊二酸(α-KG)。突变的IDH能催化α-KG转化为2-羟基戊二酸(2-HG),2-HG不是体内正常的代谢产物,高浓度的2-HG与急性髓系白血病(AML)及各种肿瘤的发生紧密相关。针对IDH突变的抑制剂能显著降低2-HG的水平,成为一些肿瘤药物开发的热点。综述IDH突变在AML和肿瘤中的作用及目前在研IDH突变体抑制剂的研究进展。
As an important enzyme of metabolic processes in human body, isocitrate dehydrogenase （IDH） is involved in the three carboxylic acid cycle and catalysis of isoeitrie acid to a-ketoglutarate. IDH mutations lead to the accumulation of （R）-2-hydroxyglutarate which is not a normal metabolite in the body. High level 2-HG is closely associated with the occurrence of leukemia and other tumors. Inhibitors of IDH mutants can reduce the level of 2-HG, and therefore have become a hot spot in the development of cancer drugs. Herein, we reviewed the role of IDH mutation in tumors and the advances in the research of mutant IDH inhibitors.
作者
黄禾
刘晓蓉
尤启冬
HUANG He;LIU Xiaorong;YOU Qidong(School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China;, Nanjing Sanhome Pharmaceutical Co.,Ltd.,R＆D Center, Nanjing 210038, China)
出处
《药学进展》
CAS
2018年第3期207-213,共7页
Progress in Pharmaceutical Sciences
