AZD 9291

一种突变型EGFR的抑制剂（对EGFRL858R/T790M、EGFRL858R和EGFRL861Q的IC50分别为1、12和5 nM）；相较于野生型EGFR（IC50 = 184 nM），对这些突变型EGFR具有选择性，同时在1 µM浓度下对约280种其他激酶无显著抑制作用；选择性抑制含有激活和/或耐药性EGFR突变的非小细胞肺癌（NSCLC）细胞的增殖（IC50 = 8-40 nM），而对含野生型EGFR的Calu-3和NCI H2073 NSCLC细胞的抑制作用较弱（IC50分别为650和461 nM）；在vandetanib耐药的PC-9 NSCLC小鼠异种移植模型中，以1-10 mg/kg剂量诱导肿瘤消退。An inhibitor of mutant EGFRs (IC50s = 1, 12, and 5 nM for EGFRL858R/T790M, EGFRL858R, and EGFRL861Q, respectively); selective for these mutant EGFRs over wild-type EGFR (IC50 = 184 nM), as well as over a panel of approximately 280 other kinases at 1 µM; selectively inhibits the proliferation of NSCLC cells containing activating and/or resistant mutants of EGFR (IC50s = 8-40 nM) over wild-type EGFR-containing Calu-3 and NCI H2073 NSCLC cells (IC50s = 650 and 461 nM, respectively); induces tumor regression in a vandetanib-resistant PC-9 NSCLC mouse xenograft model at doses ranging from 1-10 mg/kg.