AGI-5198 (135526-35-0) is a potent (IC50?= 70 nM) inhibitor of mutant isocitrate dehydrogenase 1(IDH1).1? It is selective for the R132H-IDH1 mutant and does not affect wild type cells.2? This mutation results in loss-of-function for oxidative decarboxylation of isocitrate and gain-of-function for production of the oncometabolite R-2-hydroxyglutarate (R-2HG) from alpha-ketoglutarate (2-OG).
AGI5198 inhibits mutant IDH1 (isocitrate dehydrogenase 1) in cancer cells which delays growth and promotes differentiation of the glioma cells.
AGI-5198 has been used as a negative control in ligand dilution series.
In human chondrosarcoma cell line JJ012, AGI-5198 promotes apoptosis and G2/M cell cycle arrest. It also prevents the generation of colony in chondrosarcoma cell lines. AGI-5198 hinders the multiplication of cell and induces demethylation of H3K9me3 and H3K27me3.
1) Popovici-Muller?et al. (2012),?Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG In Vivo; ACS Med. Chem. Lett.,?3?850
2) Rohle?et al. (2013),?An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells; Science,?340?626
