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http://dx.doi.org/10.5483/BMBRep.2015.48.5.021

Isocitrate dehydrogenase mutations: new opportunities for translational research  

Keum, Young-Sam (College of Pharmacy, Dongguk University)
Choi, Bu Young (Department of Pharmaceutical Science and Engineering, Seowon University)
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BMB Reports / v.48, no.5, 2015 , pp. 266-270 More about this Journal
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. [BMB Reports 2015; 48(5): 266-270]
Keywords
Cancer Metabolism; Isocitrate dehydrogenases (IDHs); Isocitrate (ICT); α-ketoglutarate (α-KG); (R)-2-hydroxyglutarate (R-2HG);
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