生物活性

• 描述FAK (Focal adhesion kinase), a non-receptor tyrosine kinase, can regulate the cytoskeleton and act as a scaffolding and signaling protein for other adhesion molecules. The expression of FAK and its phosphorylation status show a strong correlation with the invasive phenotype of aggressive human tumors. GSK2256098 is a selective FAK inhibitor with Ki value of 0.4nM. Cellular study showed that GSK2256098 inhibited p-FAK with IC50 values ranging in 2-15nM while only showed effective on cell growth inhibition in cell lines in anchorage-independent conditions with soft agar or methylcellulose, but not in standard conditions on tissue culture plastic in tested^[1]. Another study showed that GSK2256098 could dose-dependently inhibit FAK activity on its phosphorylation site with different potency according to different PDAC cells, most potent to L3.6P1 and least potent to PANC-1 cells, at concentration ranging in 0.1-10μM, as well as promote apoptosis in L3.6P1 cells through caspase-9/PARP, but showed inhibition of cell growth only in anchorage-independent manner. In vitro wound healing assays showed that pre-treatment with GSK2256098 at concentration ranging in 1-25μM for 48h caused impairment of cell motility dose-dependently in L3.6P1 and PANC-1 cells^[2]. Oral administration of GSK2256098 caused dose-dependent reduction of pFAK with maximal reduction corresponding to the Cmax of GSK2256098 in mice bearing subcutaneous human tumors, suggesting the good pharmacodynamics of GSK2256098^[1].
• 作用机制GSK2256098 is an ATP competitive inhibitor which can bound in the ATP binding pocket of FAK.^[1]

• 动物研究
  剂量	Nude Mice: 75 mg/kg[2] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02523014	Intracranial Meningioma ... more >> Recurrent Meningioma NF2 Gene Mutation Collapse <<	Phase 2	Suspended(No arms are currentl... more >>y open to patient registration) Collapse <<	-	-
  NCT01138033	Cancer	Phase 1	Completed	-	Australia, Victoria ... more >> GSK Investigational Site Heidelberg, Victoria, Australia, 3084 Australia, Western Australia GSK Investigational Site Nedlands, Western Australia, Australia, 6009 France GSK Investigational Site Caen Cedex 9, France, 14033 GSK Investigational Site Villejuif, France, 94805 United Kingdom GSK Investigational Site Glasgow, United Kingdom, G61 1BD GSK Investigational Site London, United Kingdom, NW1 2BU GSK Investigational Site London, United Kingdom, W12 0HS GSK Investigational Site London, United Kingdom, W1G 6AD GSK Investigational Site Manchester, United Kingdom, M20 4BX GSK Investigational Site Newcastle upon Tyne, United Kingdom, NE7 7DN Collapse <<
  NCT01938443	Cancer	Phase 1	Completed	-	France ... more >> GSK Investigational Site Villejuif Cedex, France, 94805 United Kingdom GSK Investigational Site London, United Kingdom, W12 0HS GSK Investigational Site London, United Kingdom, W1G 6AD GSK Investigational Site Newcastle upon Tyne, United Kingdom, NE7 7DN Collapse <<

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• 参考文献

• [1] Zhang J, He DH, et al. A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9.