The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors

Author(s): Jiao Chen, Jie Yang, Peng Cao

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 16 , Issue 16 , 2016

Become EABM
Become Reviewer
Call for Editor


Isocitrate dehydrogenase (IDH) is a metabolic enzyme that converts isocitrate to α-ketoglutarate (α-KG). Genetic gain-of-function mutations in IDH1 and IDH2 confer a neomorphic activity that allow reduction of α -KG to (R)-2- hydroxyglutarate, the accumulation of which results in the development of cancers like low grade gliomas and leukemia. After treatment with AG-221 in clinical trials, a first-in-class inhibitor of mutated IDH2, 29 patients with acute myeloid leukemia or myelodysplastic syndrome experience complete remissions and the overall response rate is 59/159 (37%). Thus, IDH mutants have become intriguing targets for cancer therapeutics. In addition to providing a brief summary of IDH mutations, this review describes known inhibitors with potential activities against IDH mutants such as AG-120, AG-221, AG-881 and AGI-6780. The evolving landscape of IDH mutant inhibitors provides us an outlook on the discovery of novel, safer, and more effective cancer treatment strategies.

Keywords: Cancer, drug discovery, IDH1, IDH2, inhibitor, mutant.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2016
Page: [1344 - 1358]
Pages: 15
DOI: 10.2174/1389557516666160609085520
Price: $65

Article Metrics

PDF: 96
HTML: 10
PRC: 1