GDC-0575

一种Chk1抑制剂（IC₅₀=1.2nM），对超过450种野生型和突变激酶的选择性超过30倍；在HL-60、KG-1、U937和ML-1急性髓系白血病（AML）细胞中增强阿糖胞苷诱导的细胞凋亡；在AML患者来源的异种移植（PDX）小鼠模型中，与阿糖胞苷联合使用时，以7.5mg/kg剂量几乎完全消除肿瘤负荷。A Chk1 inhibitor (IC50 = 1.2 nM); >30-fold selective for Chk1 over a panel of more than 450 wild-type and mutant kinases; enhances cytarabine-induced apoptosis in HL-60, KG-1, U937, and ML-1 AML cells; nearly completely eliminates tumor burden in AML PDX mouse models at 7.5 mg/kg in combination with cytarabine.分子式C16H20BrN5O分子量378.3O=C(C1CC1)NC2=CNC3=NC=C(Br)C(N4C[C@@H](CCC4)N)=C23