PF-06873600

一种CDK2、CDK4和CDK6的抑制剂，对CDK2、CDK4和CDK6的抑制常数（Ki）分别为0.13nM、1.25nM和0.11nM。该化合物对CDK4和CDK6的选择性高于CDK1和CDK9，后者的Ki值分别为4.5nM和19.6nM。在OVCAR-3卵巢癌细胞中，该化合物抑制RB1蛋白的磷酸化，并抑制细胞增殖，其EC50值分别为19nM和45nM。此外，该化合物在体外抑制MDA-MB-468细胞的生长，GI50值为2.2µM。在CTG-0464和CTG-01912非小细胞肺癌（NSCLC）患者来源的异种移植（PDX）小鼠模型中，以30mg/kg的剂量给药可显著减少肿瘤体积。An inhibitor of Cdk2, Cdk4, and Cdk6 (Kis = 0.13, 1.25, and 0.11 nM, respectively); selective for these CDKs over Cdk1 and Cdk9 (Kis = 4.5 and 19.6 nM, respectively); inhibits the phosphorylation of RB1 in, and the proliferation of, OVCAR-3 ovarian cancer cells (EC50s = 19 and 45 nM, respectively); reduces tumor volume in CTG-0464 and CTG-01912 NSCLC PDX mouse models at 30 mg/kg.分子式C20H27F2N5O4S分子量471.5O=C1N([C@@]2([H])[C@](O)(CCC2)C)C3=NC(NC4CCN(CC4)S(C)(=O)=O)=NC=C3C=C1C(F)F