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 ...
[Ornstein, Paul L.; Schaus, John M.; Chambers, John W.; Huser, Diane L.; Leander, J. David; et al. Journal of Medicinal Chemistry, 1989 , vol. 32, # 4 p. 827 - 833]
