生物活性

• 靶点

  PDGFRβ IC50:2nM

  VEGFR2 IC50:80nM

• 描述VEGFR (vascular endothelial growth factor) and PDGFR (platelet-derived growth factor receptor) are critical roles in tumor growth and suvival via autocrine and paracrine loops, making them the well validated targets for the treatment of cancers. Sunitinib is a multiple RTKs inhibitor with IC50 values of 2nM and 80nM for VEGFR2 and PDGFRβ (measured by kinase activity)^[1], respectively, also shows inhibition against KIT and FLT3 receptor^[2]. The cellular kinase activity induced by VEGF/PDGF can be inhibited by Sunitinib with IC50 value of 5-50nM/10nM in 3T3 cells, while the PDGF-induced cell growth can be inhibited by Sunitinib with IC50 of 8nM^[1]. Daily oral administration of Sunitinib at dose of 80mg/kg reduced growth of established SF763T tumor xenografts in athymic mice, as well as suppressed Colo205 tumor growth. Consistent with the cellular kinase study, the inhibition by Sunitinib against p-PDGFRβ can be observed in tumor after a single dose at 80mg/kg in mice bearing SF767T tumors and mice bearing Colo205 tumors, as well as suppressed p-FLK1 in A375 xenograft mice dosed 40mg/kg Sunitinib^[2].
• 作用机制Sunitinib is an ATP-competitive multitargeted tyrosine kinase inhibitor.^[3]

• 动物研究
  剂量	Rat: 0.5 mg/kg[5] (p.o.), 1 mg/kg - 10 mg/kg[6] (p.o.) Mice: 40 mg/kg[7] (p.o.)
  给药途径	p.o.