AGI-5198

AGI-5198 (also know as IDH-C35) is a potent and selective mutant IDH1 inhibitor. AGI-5198 has been shown to have anti-tumor efficacy in the TS603 glioma cell line and to lower tumor 2-HG production in HT1080 and U87MG cells with IC50 values of 0.48 μM and 0.07 μM, respectively. AGI-5198 (IDH-C35) inhibits IDH1 R132H mutant and R132C mutant in vitro with IC50 of 0.07 μM and 0.16 μM respectively, but not wild-type IDH1 or any of the examined IDH2 isoforms (IC50 > 100 μM). In R132H-IDH1 glioma xenografts, AGI-5198 (450 mg/kg/day) caused 50-60% growth inhibition over a treatment period of three weeks with no affect in the growth of IDH1 wild-type glioma xenografts. Under conditions of near complete 2-HG inhibition, AGI-5198 can induce demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation.