生物活性

• 靶点	FGFR IC50:52.4nM

• 描述The FGFR (fibroblast growth factor receptor) family comprises four members, FGFR1, FGFR2, FGFR3 and FGFR4, ligand of which can induce cellular phosphorylation events, proliferation and potent antiangiogenic activity. PD166866 is a highly selective and nanomolar potent inhibitor of FGFR-1 tyrosine kinase with an IC50 value of 52.4nM (measure protein tyrosine kinase activity) and no effect on c-Src, platelet-derived growth factor receptor-b, EGFR or insulin receptor tyrosine kinases or on MAPK, PKC and CDK4 at concentrations as high as 50μM. Pre-treatment with PD 166866 on concentration of 10 or 100nM for 2h caused inhibition on autophosphorylation of FGFR1 induced by bFGF (25ng/ml) for 5 min in NIH 3T3 cells expressing endogenous FGFR1 and in L6 cells overexpressing the human FGFR1 tyrosine kinase, along with the inhibition of downstream p-ERK 1/2. Consistent with this, daily exposure to PD 166866 at concentrations 1-100nM for 8 consecutive days resulted in a concentration-related inhibition of bFGF-stimulated cell growth of L6 cells^[1]. Another mechanism action of PD166866 on negative control of cell proliferation maybe due to its activation of the apoptotic pathway, suggested by specific point as evaluation of DNA damage, lipoperoxidation of the cell membrane and increase of expression of PARP, an enzyme directly involved in DNA repair^[2].
• 作用机制PD 166866 is an ATP competitive inhibitor of FGFR1.^[1]

• 动物研究
  剂量	Mice[3] (i.p.): 20 mg/kg
  给药途径	i.p.