BAY-1436032

BAY-1436032 is an inhibitor of mutant isocitrate dehydrogenase 1 (IDH1, IC50 = 0.015 µM for both IDH1R132H and IDH1R132C). It is selective for mutant IDH1 over wild-type IDH1 and IDH2 (IC50s = 20 and >100 µM, respectively). BAY-1436032 inhibits production of alpha-hydroxyglutaric acid (2-HG, Cay-25894, Cay-16374) in HEK293 cells expressing IDH1R132H, IDH1R132C, IDH1R132G, IDH1R132S, and IDH1R132L, but not IDH1R100Q, IDH2R172K, IDH2R172W, or IDH2R172M. It also inhibits 2-HG production in LN-229 glioblastoma and HCT116 colorectal carcinoma cells overexpressing IDH1R132H (IC50s = 73 and 47 nM, respectively), as well as in HT-1080 sarcoma cells endogenously expressing IDH1R132C (IC50 = 135 nM). BAY-1436032 (150 mg/kg) reduces tumor growth and increases survival in an NCH551b IDH1R132H mutant secondary glioblastoma patient-derived xenograft (PDX) mouse model. It also induces myeloid differentiation of IDH1R132C mutant acute myeloid leukemia (AML) cells in mice when administered at doses of 45 and 150 mg/kg.Formal Name: 2-[[4-(trifluoromethoxy)phenyl]amino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]-1H-benzimidazole-5-propanoic acid. CAS Number: 1803274-65-8. Molecular Formula: C26H30F3N3O3. Formula Weight: 489.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 1 mg/ml, DMSO: 3 mg/ml, Ethanol: 3 mg/ml. lambdamax: 295 nm. SMILES: OC(CCC1=CC=C2N([C@@]3([H])CC(C)(C[C@H](C3)C)C)C(N([H])C4=CC=C(C=C4)OC(F)(F)F)=NC2=C1)=O. InChi Code: InChI=1S/C26H30F3N3O3/c1-16-12-19(15-25(2,3)14-16)32-22-10-4-17(5-11-23(33)34)13-21(22)31-24(32)30-18-6-8-20(9-7-18)35-26(27,28)29/h4,6-10,13,16,19H,5,11-12,14-15H2,1-3H3,(H,30,31)(H,33,34)/t16-,19+/m0/s1. InChi Key: RNMAUIMMNAHKQR-QFBILLFUSA-N.