1429179-07-6

IDH889 is a potent and selective inhibitors of IDH1. IDH899 shows IDH (R132H) IC50 = 20 nM; Cell 2-HG IC50 = 14 nM. IDH889 demonstrates significantly improved plasma exposure in mice vs IDH662 (AUC 3.6 μM·h, Cmax 1.7 μM at 10 mg/kg; AUC 55.5 μM·h, Cmax 14.2 μM at 100 mg/kg). IDH889 also has excellent permeability and no efflux in the Caco-2 and human MDR1-MDCK cell lines, supporting the hypothesis that potent inhibition of mutant IDH1 function by binding at the allosteric binding site is compatible with brain penetration.

IDH889 是一种可口服利用的，脑渗透性的，变构和突变特异性的异柠檬酸脱氢酶 (IDH1) 抑制剂。IDH889 对 IDH1 R132* 突变型具有高效选择性，对 IDH1R132H、IDH1R132C 和 IDH1wt 作用的 IC50 值分别为 0.02 μM, 0.072 μM 和 1.38 μM。IDH889 具有高效的细胞内 2-HG 水平抑制作用，其 IC50 值为 0.014 μM。