title: Isocitrate dehydrogenase mutations: new opportunities for translational research.
abstract: Over the last decade, comprehensive genome-wide sequencing studies have enabled us to find out unexpected genetic alterations of metabolism in cancer. An example is the identification of arginine missense mutations of isocitrate dehydrogenases-1 and -2 (IDH1/2) in glioma, acute myeloid leukemia (AML), chondrosarcomas, and cholangiocarcinoma. These alterations are closely associated with the production of a new stereospecific metabolite, (R)-2-hydroxyglutarate (R-2HG). A large number of follow-up studies have been performed to address the molecular mechanisms of IDH1/2 mutations underlying how these events contribute to malignant transformation. In the meanwhile, the development of selective mutant IDH1/2 chemical inhibitors is being actively pursued in the scientific community and pharmaceutical industry. The present review article briefly discusses the important findings that highlight the molecular mechanisms of IDH1/2 mutations in cancer and provides a current status for development of selective mutant IDH1/2 chemical inhibitors.
authors: College of Pharmacy, Dongguk University, Goyang 410-820, Korea.
authors: Young-Sam
authors: YS
authors: Keum
authors: Department of Pharmaceutical Science and Engineering, Seowon University, Cheongju 361-742, Korea.
authors: Bu Young
authors: BY
authors: Choi
mesh_terms: D001120:Arginine / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005977:Glutarates / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics*; D020125:Mutation, Missense; D009369:Neoplasms / Q000201:enzymology; D057170:Translational Research, Biomedical
chemical_list: D004791:Enzyme Inhibitors; D005977:Glutarates; D007527:Isoenzymes; C019417:alpha-hydroxyglutarate; D001120:Arginine; D007521:Isocitrate Dehydrogenase