DS-1001b

DS-1001b is an inhibitor of mutant isocitrate dehydrogenase 1 (IDH1, IC50s = 15 and 130 nM for IDH1R132H and IDH1R132C, respectively). It is selective for mutant IDH1, which converts alpha-ketoglutarate to the oncometabolite 2-hydroxyglutarate (2-HG), over wild-type IDH1 and IDH2, which convert isocitrate to alpha-ketoglutarate, as well as IDH2R140Q and IDH2R172Q (IC50s = >10,000 nM for all). DS-1001b inhibits 2-HG production in TF-1 cells stably transfected with IDH1R132H or IDH1R132C (IC50s = 29 and 35 nM, respectively) and in 293A cells transiently transfected with IDH1R132H or IDH1R132C (IC50s = 29 and 42 nM, respectively). DS-1001b reduces tumor growth, as well as intratumoral and plasma 2-HG levels, in a subcutaneous IDH1R132H-expressing A1074 patient-derived xenograft (PDX) mouse model of glioblastoma.Formal Name: (2E)-3-[1-[[5-(1-fluoro-1-methylethyl)-3-(2,4,6-trichlorophenyl)-4-isoxazolyl]carbonyl]-3-methyl-1H-indol-4-yl]-2-propenoic acid, compd. with 2-methyl-2-propanamine (1:1). CAS Number: 1898207-64-1. Molecular Formula: C25H18Cl3FN2O4 . C4H11N. Formula Weight: 608.9. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 1 mg/ml, DMSO: 1 mg/ml, Ethanol: 1 mg/ml. lambdamax: 316 nm. SMILES: CC(C)(N)C.CC1=CN(C(C2=C(C(C)(F)C)ON=C2C3=C(Cl)C=C(Cl)C=C3Cl)=O)C4=CC=CC(/C=C/C(O)=O)=C41. InChi Code: InChI=1S/C25H18Cl3FN2O4.C4H11N/c1-12-11-31(17-6-4-5-13(19(12)17)7-8-18(32)33)24(34)21-22(30-35-23(21)25(2,3)29)20-15(27)9-14(26)10-16(20)28,1-4(2,3)5/h4-11H,1-3H3,(H,32,33),5H2,1-3H3/b8-7+,. InChi Key: UPPAAWQBZQBNIE-USRGLUTNSA-N.