AGI-5198 | R132 mutant isocitrate dehydrogenase inhibitor

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).

References/Citations

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