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|
NVP-ACC789 is an inhibitor of human VEGFR-1, VEGFR-2 (mouse VEGFR-2), VEGFR-3 and PDGFR-β with IC50s of 0.38, 0.02 (0.23), 0.18, 1.4 μM, respectively.
|EG00229 Trifluoroacetate salt
EG00229 Trifluoroacetate is the first small molecule inhibitor of the neuropilin-1 and VEGF-A interaction with an IC50 of inhibition of 8 uM (125I-VEGF binding to PAE/NRP1 cells).
Apatinib is a selective VEGFR2 inhibitor with IC50 of 1 nM.
JI-101 is an orally available multi-kinase inhibitor of VEGFR2，PDGFRβ and EphB4 with potential antiangiogenic and antineoplastic activities.
BAW2881 (NVP-BAW2881) is a potent and selective VEGFR2 inhibitor with activity to inhibit chronic and acute skin inflammation.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.