Does mIDH Inhibitors is a Promising Therapy?

IDH are family of enzymes that comprises three proteins, IDH1, IDH2 and IDH3. IDH1 is located in the cytoplasm while IDH2 and IDH3 are located in the mitochondria [1,2]. The IDHs are tricycle carboxylic acid cycle enzymes which convert isocitrate to α-KG via oxidative decarboxylation, producing NADPH (IDH1 and 2) and NADH (IDH3) [3]. IDH proteins are involved in diverse cellular processes including adaptation to hypoxia, histone demethylation and DNA modification [4]. Mutations have only been identified in IDH1 and IDH2 gene [3]. The mutated IDH1 and IDH2 proteins have a gain of function, neomorphic activity, catalyzing the reduction of α-KG to 2-HG [5]. The abnormal production of the oncometabolite 2-HG promote tumorigenesis [5]. IDH1/2 mutations define distinct subsets of cancers, including low-grade gliomas, secondary glioblastomas, chondrosarcomas, intrahepatic cholangiocarcinomas, and hematologic malignancies [6].