生物活性

• 靶点

  FGFR1 IC50:~25nM

  VEGFR2 IC50:100nM-200nM

• 描述Angiogenesis, playing a major role in the progression of human diseases such as diabetic retinopathy, atherosclerosis and cancer, involves the concerted action of a number of polypeptide factors such as VEGF, Ang1 and FGF. PD173074 is a selective dual inhibitor of both FGFR1 and VEGFR2 with IC50 value of 21.5nM (measured by kinase activity) and 100-200nM (measured by VEGFR2 auto-phosphorylation in NIH 3T3 cells), respectively. PD173074 inhibited auto-phosphorylation of FGFR1, induced by aFGF and heparin, of NIH-3T3 cells expressing FGFR1 endogenously in a dose-dependent manner with an IC50 in the range 1–5nM, as well as auto-phosphorylation of overexpressed VEGFR2 stimulated with VEGF (100ng/ml) with an IC50 of 100–200nM. Mice treated daily with PD173074 by intraperitoneal injection per day starting 3 days prior to pellet implantation exhibited inhibition of bFGF-induced neovascularization by 86% at a dose of 1mg/kg, as well as inhibition of VEGF induced neovascularization by 81% at a dose of 2mg/kg^[1]. PD173704 can specifically and effectively inhibit multiple FGF-2-mediated responses of both oligodendrocyte progenitors, as well as differentiated oligodendrocytes with complete antagonization on two phenotypic alterations, downregulation of myelin proteins, and their re-entry into the cell cycle^[2].
• 作用机制PD173074 is an ATP-competitive inhibitor of FGFR1.^[1]

• 动物研究
  剂量	Nude Mice[3]: 12 mg/kg Mice: 1 mg/kg, 2 mg/kg[1] (i.p.), 25 mg/kg - 100 mg/kg[4] (p.o.)
  给药途径	i.p., p.o.