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 Malate is the Malate form of Sunitinib. 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.
  动物药代数据	Animal Rats[8] Dose 2 mg/kg (i.v. or p.o.) Administration i.v. p.o. F 112 ± 34% (p.o.) T1/2 2.52 ± 0.04 h (i.v.) AUCtlast 896 ± 461 ng·h/ml (p.o.) Tmax 2.0 ± 2.0 h (p.o.) Cmax 177 ± 86 ng/ml (p.o.) AUC0→∞ 996 ± 439 ng·h/ml (i.v.) 1178 ± 691 ng·h/ml (p.o.) CLs 40 ± 23 ml/min/kg (i.v.)