GW843682X

一种可逆的、可穿透细胞的PLK抑制剂；在无细胞测定中，选择性抑制Plk1和Plk3（IC50s=2.2和9.1nM），抑制率超过30种其他激酶；使用嵌合Plk1报告基因测定，体外抑制HeLa细胞中的Plk1活性（IC50=0.14μM）；抑制一组中九种癌细胞系的生长（IC50s=0.11-0.7μM），但不抑制PC3人前列腺癌细胞（IC50=6.82μM）或非癌性人二倍体成纤维细胞（HDF；IC50=6.14µM）；抑制MES-SA人子宫肉瘤细胞以及耐药、表达P糖蛋白的MES-SA/Dx5亚系的生长（IC50s分别为0.21和0.21μM）；抑制患者来源的白血病细胞的生长（IC50s=2/M细胞周期停滞和H460人肺癌、PALL-2和MOLM13人白血病癌细胞的凋亡，且呈浓度依赖性。A reversible, cell-permeable PLK inhibitor; selectively inhibits Plk1 and Plk3 (IC50s = 2.2 and 9.1 nM, respectively) over more than 30 other kinases in a cell-free assay; inhibits Plk1 activity in vitro in HeLa cells using a chimeric Plk1 reporter assay (IC50 = 0.14 μM); inhibits growth in nine cancer cell lines in a panel (IC50s = 0.11-0.7 μM) but not of PC3 human prostate cancer cells (IC50 = 6.82 μM) or non-cancerous human diploid fibroblasts (HDFs; IC50 = 6.14 µM); inhibits growth of MES-SA human uterine sarcoma cells, as well as of the drug-resistant, P-glycoprotein-expressing MES-SA/Dx5 subline (IC50s = 0.21 and 0.21 μM, respectively); inhibits the growth of patient-derived leukemia cells (IC50s = 2/M cell cycle arrest and apoptosis of H460 human lung and PALL-2 and MOLM13 human leukemia cancer cells in a concentration-dependent manner.