生物活性

• 靶点

  VEGFR1 IC50:10nM

  c-Kit IC50:140nM

  c-FMS IC50:146nM

  VEGFR2 IC50:30nM

  VEGFR3 IC50:47nM

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• 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 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
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  Daudi cell	-	Growth inhibition assay	-	Inhibition of human LB1047-RCC cell growth in a cell viability assay, IC50=3.53164 μM	SANGER
  human A172 cell	-	Growth inhibition assay	-	Inhibition of human A172 cell growth in a cell viability assay, IC50=3.7379 μM	SANGER
  human A204 cell	-	Growth inhibition assay	-	Inhibition of human A204 cell growth in a cell viability assay, IC50=109.06 nM	SANGER

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• 动物研究
  剂量	Mice: 30 mg/kg - 100 mg/kg[3] (p.o., BID)
  给药途径	p.o.
  动物药代数据	Animal Rats[4] Dogs[4] Monkeys[4] Dose 10 mg/kg 1 mg/kg 5 mg/kg Administration i.v. or p.o. i.v. or p.o. i.v. or p.o. F 72% (p.o.) 47% (p.o.) 49% (p.o.) T1/2 3.6 h (i.v.) 2.2 h (i.v.) 4.7 h (i.v.) CL 1.7 ml/min/kg (i.v.) 1.4 ml/min/kg (i.v.) 1.6 ml/min/kg (i.v.) Vdss 0.478 L/kg (i.v.) 0.297 L/kg (i.v.) 0.283 L/kg (i.v.)

• 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 ... more >> 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 Collapse <<
  NCT01027598	-	-	Completed	-	-
  NCT01407562	Unspecified Adult Solid Tumor ... more >>- Protocol Specific Breast Cancer - Female Collapse <<	Phase 1	Active, not recruiting	June 2019	United States, New Jersey ... more >> Rutgers Cancer Institute of New Jersey New Brunswick, New Jersey, United States, 08903 Collapse <<

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