产品说明书

Pazopanib HCl

Print
Chemical Structure| 635702-64-6 同义名 : GW786034 Hydrochloride;Pazopanib HCl;GW786034 HCl
CAS号 : 635702-64-6
货号 : A623193
分子式 : C21H24ClN7O2S
纯度 : 99+%
分子量 : 473.979
MDL号 : -
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(18.99 mM)，配合低频超声助溶，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：

30% PEG400+0.5% Tween80+5% propylene glycol+water 30 mg/mL suspension

生物活性
描述 VEGF/VEGFR (vascular endothelial growth factor vascular endothelial growth factor receptor) pathway plays a key role in tumor angiogenesis by promotion of vascular and lymphatic endothelial, as well as survival, and invasion, thus resulting in neovascularization, tumor growth and metastasis. In addition, blockade of additional proangiogenic receptor tyrosine kinases, including PDGFR and FGFR, may improve long-term clinical outcomes. Pazopanib hydrochloride is the hydrochloride form of Pazopanib. Pazopanib is a pan VEGFR inhibitor with IC50 values of 10nM, 30nM and 47nM for VEGFR1, VEGFR2 and VEGFR3 (measured by HTRF), respectively, less potent to c-Kit, PDGFR, FGFR and c-Fms with IC50 values of 74nM, 84nM, 140nM and 146nM. In cellular studies, Pazopanib inhibited VEGF/bFGF-induced proliferation of HUVECs with IC50 value of 21nM/720nM, as well as potently inhibited VEGF-induced the phosphorylation of VEGFR-2 with IC50 value of ∼8nM. As prediction by the inhibition of VEGFR and FGFR, matrigel plug assay showed that once-daily oral administration of Pazopanib at dose of 30mg/kg and 100mg/kg inhibited angiogenesis by 57% and 83%, respectively, in female swiss nu/nu mice, as well as achieved tumor inhibition by 32%, 59% and 69% in HT29 xenograft, 16%, 35% and 55% in A375P xenograft, 99%, 102% and 110% in HN5 xenograft at dose of 10mg/kg, 30mg/kg and 100mg/kg[1].
作用机制 Pazopanib is an ATP-competitive inhibitor of human VEGFR2.[2]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
5637 Growth inhibitory assay IC50=15.0 μM 23887605
5637 20 μM Autophagy assay triggers the autophagic process 23887605
5637 20 μM Function assay induces lysosomal-dependent necrosis 23887605
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01027598 Non Small Cell Lung Cancer Phase 2 Completed - United States, Florida ... 展开 >> Florida Cancer Specialists Fort Myers, Florida, United States, 33901 United States, Georgia Suburban Hem Onc Lawrenceville, Georgia, United States, 30045 United States, Ohio Oncology Hematology Care Cincinnati, Ohio, United States, 45242 United States, South Carolina South Carolina Oncology Associates, PA Columbia, South Carolina, United States, 29210 United States, Tennessee Chattanooga Oncology Hematology Associates Chattanooga, Tennessee, United States, 37404 Family Cancer Center Collerville, Tennessee, United States, 38119 Tennessee Oncology, PLLC Nashville, Tennessee, United States, 37023 United States, Virginia Virginia Cancer Institute Richmond, Virginia, United States, 23235 收起 <<
NCT00788580 Unspecified Adult Solid Tumor,... 展开 >> Protocol Specific 收起 << Phase 1 Withdrawn(Study was discontinu... 展开 >>ed.) 收起 << - -
NCT01027598 - Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.11mL

0.42mL

0.21mL

10.55mL

2.11mL

1.05mL

21.10mL

4.22mL

2.11mL
参考文献

[1]Harris PA, Boloor A, et al. Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino] -2-pyrimidinyl] amino] -2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J Med Chem. 2008 Aug 14;51(15):4632-40.

[2]Kumar R, Knick VB, et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther. 2007 Jul;6(7):2012-21.

[3]Wang YK, Yang XN, et al. A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice. Xenobiotica. 2019 Jun;49(6):655-670.