PKI-166

一种EGFR抑制剂（IC50=0.0007µM，针对细胞内激酶域）；对EGFR细胞内激酶域的选择性高于丝氨酸/苏氨酸激酶PKC-α和Cdc2/cyclin B（IC50分别为>100和78µM），以及FLK、c-Met和Tek（IC50均为>1µM），但确实抑制c-Src、c-Abl、VEGFR2/KDR、FLT1和c-Kit（IC50分别为0.103、0.028、0.327、0.962和2.21µM）；增强吉美替滨在L3.6pl细胞中的细胞毒性；在L3.6pl小鼠异种移植模型中以100mg/kg的剂量减少肿瘤生长和转移，并在与吉美替滨联合使用时具有加成效应；在SN12-PM6人肾细胞癌小鼠原位模型中减少肿瘤生长并抑制血管生成。An inhibitor of EGFR (IC50 = 0.0007 µM for the intracellular kinase domain); selective for the EGFR intracellular kinase domain over the serine/threonine kinases PKC-α and Cdc2/cyclin B (IC50s = >100 and 78 µM, respectively), as well as FLK, c-Met, and Tek (IC50 = >1 µM for all), but does inhibit c-Src, c-Abl, VEGFR2/KDR, FLT1, and c-Kit (IC50s = 0.103, 0.028, 0.327, 0.962, and 2.21 µM, respectively); enhances the cytotoxicity of gemcitabine in L3.6pl cells; reduces tumor growth and metastasis and increases survival in an L3.6pl mouse xenograft model at 100 mg/kg per day with additive effects when administered in combination with gemcitabine; reduces tumor growth and inhibits angiogenesis in an SN12-PM6 human renal cell carcinoma mouse orthotopic model.