Description
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).
Uses
AGI5198 inhibits mutant IDH1 (isocitrate dehydrogenase 1) in cancer cells which delays growth and promotes differentiation of the glioma cells.
Uses
AGI-5198 has been used as a negative control in ligand dilution series.
Biochem/physiol Actions
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.
References
[1] JANETA POPOVICI-MULLER*. Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo[J]. ACS Medicinal Chemistry Letters, 2012, 3 10: 850-855. DOI:
10.1021/ml300225h[2] DAN ROHLE. An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells[J]. Science, 2013, 340 6132. DOI:
10.1126/science.1236062
