DS-1001b

一种突变型IDH1抑制剂（对IDH1R132H和IDH1R132C的IC50值分别为15nM和130nM）；对突变型IDH1的选择性高于野生型IDH1和IDH2，以及IDH2R140Q和IDH2R172Q（对这些酶的IC50均>10,000nM）；在稳定转染IDH1R132H或IDH1R132C的TF-1细胞中抑制2-HG的产生（IC50值分别为29nM和35nM），以及在瞬时转染IDH1R132H或IDH1R132C的293A细胞中抑制2-HG的产生（IC50值分别为29nM和42nM）；在表达IDH1R132H的A1074患者来源的异种移植（PDX）小鼠胶质母细胞瘤模型中，减少肿瘤生长以及肿瘤内和血浆中的2-HG水平。An inhibitor of mutant IDH1 (IC50s = 15 and 130 nM for IDH1R132H and IDH1R132C, respectively); selective for mutant IDH1 over wild-type IDH1 and IDH2, as well as IDH2R140Q and IDH2R172Q (IC50s = >10,000 nM for all); 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); reduces tumor growth, as well as intratumoral and plasma 2-HG levels, in a subcutaneous IDH1R132H-expressing A1074 PDX mouse model of glioblastoma.分子式C25H18Cl3FN2O4 • C4H11N分子量608.9CC(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