Pazopanib is an oral angiogenesis inhibitor of tyrosine kinases, targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. Two clinical trials met the inclusion criteria for the use of pazopanib in RCC (a Phase II and a Phase III trial). Pazopanib is an inhibitor of numerous tyrosine kinases, including vascular endothelial growth factor receptor and platelet-derived growth factor receptors. It is involved in inhibiting signaling pathways, angiogenesis, and cell proliferation. A 2-fold increase in AUC was seen when pazopanib was administered with a high-fat meal as well as when crushing the tablet. Thus, pazopanib should be administered on an empty stomach at least 1 hour before or 2 hours after a meal. Pazopanib is primarily metabolized by cytochrome P-450 3A4, and caution should be used with concomitant administration of cytochrome P-450 inducers and/or inhibitors. In a Phase III trial of pazopanib in metastatic RCC, pazopanib reportedly improved progression-free survival from a median of 4.2 to 9.2 months compared with placebo (P < 0.0001). The most common adverse effects of pazopanib were hypertension, hair depigmentation, diarrhea, nausea, anorexia, and vomiting. Many of the grade 3/4 toxicities were hepatic in nature, with elevations occurring in aspartate aminotransferase, alanine aminotransferase, and bilirubin. Pazopanib is reportedly effective in the treatment of metastatic RCC. Although there are currently no direct comparisons between pazopanib and other tyrosine kinase inhibitors, the data suggest that pazopanib may be a first-line option in the treatment of RCC. The only Phase III trial of pazopanib suggests improvement of progression-free survival in RCC as well as tolerability in the selected population.
|Cell lines||MM.1S, MM.1R, RPMI-Dox40 (Dox40), and OPM2 cells|
|Preparation method||Cell Proliferation Assay
Cell growth was assessed by measuring [3H]thymidine uptake as described.
|Incubation time||48 h|
|Animal models||MM.1S MM cells tumor xenograft mouse model in Beige-nude Xid mice|
|Formulation||0.5% hydroxypropylmethyl cellulose (Sigma-Aldrich, St. Louis, MO) and 0.1% Tween-80 (Sigma-Aldrich) in water|
|Dosages||30 and 100mg/kg daily|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO ≥90 mg/mL|
Liquid chromatography-tandem mass spectrometric assay for therapeutic drug monitoring of the tyrosine kinase inhibitor pazopanib in human plasma.
Sparidans et al. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Aug 10. PMID: 22917595.
Safety and tolerability of pazopanib in the treatment of renal cell carcinoma.
Zivi et al. Expert Opin Drug Saf. 2012 Sep;11(5):851-9. PMID: 22861374.
Pazopanib in advanced and platinum-resistant urothelial cancer: an open-label, single group, phase 2 trial.
Necchi et al. Lancet Oncol. 2012 Aug;13(8):810-6. PMID: 22819172.
Cytokine and angiogenic factors associated with efficacy and toxicity of pazopanib in advanced soft-tissue sarcoma: an EORTC-STBSG study.
Sleijfer et al. Br J Cancer. 2012 Aug 7;107(4):639-45. PMID: 22805326.
The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma.
Podar K, et al. Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19478-83. PMID: 17164332.
|Related VEGFR/PDGFR Products|
Regorafenib (BAY 73-4506) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively.
|Pazopanib HCl (GW786034 )
Pazopanib HCl (GW786034 HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively.
|Dovitinib (TKI-258) Dilactic Acid
Dovitinib Dilactic acid (TKI258 Dilactic acid) is the Dilactic acid of Dovitinib, which is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM.
Toceranib(SU 11654; PHA 291639) is a kinase inhibitor with both antitumor and antiangiogenic activity through inhibition of KIT, vascular endothelial growth factor receptor 2, and PDGFRβ.
|Nintedanib (BIBF 1120)
Nintedanib (BIBF 1120) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM in cell-free assays. Phase 3.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.