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Sunitinib

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Chemical Structure| 557795-19-4 同义名 : 苏尼替尼 ;SU 11248
CAS号 : 557795-19-4
货号 : A157426
分子式 : C22H27FN4O2
纯度 : 98%
分子量 : 398.47
MDL号 : MFCD09260778
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(50.19 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+water 0.2 mg/mL clear

PO 0.5% CMC-Na 34 mg/mL suspension

生物活性
靶点

  • VEGFR2

    VEGFR2, IC50:80 nM

  • VEGFR2

    VEGFR2 , IC50:80 nM

  • PDGFRβ

    PDGFRβ, IC50:2 nM

  • PDGFRβ

    PDGFRβ , IC50:2 nM

  • c-Kit
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]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
3T3 cells Function assay Inhibition of PDGF-induced BrdU incorporation in 3T3 cells with 0.1% bovine serum albumin, IC50=7 nM 12646019
3T3 cells Function assay Inhibition of Vascular endothelial growth factor receptor in 3T3 cells, IC50=50 nM 12646019
HEK293 cells Function assay Binding affinity to FLT3 catalytic domain expressed in HEK293 cells by competitive binding assay, Kd=0.47 nM 19754199
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.51mL

0.50mL

0.25mL

12.55mL

2.51mL

1.25mL

25.10mL

5.02mL

2.51mL
参考文献

[1]Sun L, Liang C, et al. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl] -2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J Med Chem. 2003 Mar 27;46(7):1116-9.

[2]Mendel DB, Laird AD, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003 Jan;9(1):327-37.

[3]Shukla S, Robey RW, et al. Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos. 2009 Feb;37(2):359-65.

[4]Zhou Q, Gallo JM. Differential effect of sunitinib on the distribution of temozolomide in an orthotopic glioma model. Neuro Oncol. 2009;11(3):301-10.