Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases: Synthesis, Structure–Activity Relationship, and Selective Antitumor Activity

Z Liu, Y Yao, M Kogiso, B Zheng, L Deng…

Index: Xue, Jian; Diao, Jiasheng; Cai, Guobin; Deng, Lisheng; Zheng, Baisong; Yao, Yuan; Song, Yongcheng ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 2 p. 278 - 282

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Citation Number: 8

Abstract

Mutations of isocitrate dehydrogenase 1 (IDH1) are frequently found in certain cancers such as glioma. Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of α-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. Several 1-hydroxypyridin-2-one compounds were identified to be inhibitors of IDH1 (R132H). A total of 61 derivatives were synthesized, and their structure–activity ...