PF-562271 besylate

FAK:1.5 nM

在多个人类皮下移植模型中，PF-562271显示出剂量依赖性的肿瘤生长抑制作用，对PC-3M、BT474、BxPc3和LoVo的最大肿瘤抑制率在每日两次，每次25至50 mg/kg剂量下，范围从78%至94%，且无体重下降、病态或死亡现象。[1] PF-562271（通过p.o.给药，25 mg/kg）在皮下和骨转移的PC3M-luc-C6移植模型中显著减缓了肿瘤进展。[3] 在Huh7.5肝细胞癌移植模型中，sunitinib和PF-562271的联合治疗针对血管生成和肿瘤侵袭性，比单一化合物治疗产生更显著的抗肿瘤效果，通过阻断肿瘤生长及影响肿瘤在撤销治疗后的恢复能力。[4]

PF-562271对FAK和Pyk2酪氨酸激酶活性表现出选择性抑制效果，其IC50分别为1.5 nM和14 nM。在基于细胞的实验中，PF-562271对FAK的IC50表现为5 nM，与其他激酶靶标相比表现出更高的选择性。[1] 在二维(2D)培养条件下，PF-562271能够依剂量依赖性抑制FAK WT、FAK/和FAK激酶缺陷(KD)细胞的增殖，其IC50分别为3.3 μM、2.08 μM和2.01 μM。[2]

Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:55 mg/mL (82.62 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Cells are plated for 48 hours before addition of PF-562271. After 3 days cells are fixed by addition of ice cold 25% trichloroacetic acid (TCA) solution prior to staining with Sulforhodamine B (SRB) dye solution. Plates are washed with 1% glacial acetic acid, air-dried and resuspended in 10 mM Tris buffer, pH 10.5 before reading absorbance at 540 nm. Curve fitting and generation of IC50 values is carried out using GraphPad Prism 4 software from six replicates.(Only for Reference)