BAY-1436032

An inhibitor of mutant IDH1 (IC50 = 0.015 µM for both IDH1R132H and IDH1R132C); selective for mutant IDH1 over wild-type IDH1 and IDH2 (IC50s = 20 and >100 µM, respectively); inhibits 2-HG production in HEK293 cells expressing IDH1R132H, IDH1R132C, IDH1R132G, IDH1R132S, and IDH1R132L; inhibits 2-HG production in LN-229 and HCT116 cells overexpressing IDH1R132H (IC50s = 73 and 47 nM, respectively), as well as in HT-1080 cells endogenously expressing IDH1R132C (IC50 = 135 nM); reduces tumor growth and increases survival in an NCH551b IDH1R132H mutant secondary glioblastoma PDX model at 150 mg/kg; also induces myeloid differentiation of IDH1R132C mutant AML cells in mice at 45 and 150 mg/kg