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Pazopanib-d6 is intended for use as an internal standard for the quantification of pazopanib by GC- or LC-MS. Pazopanib is a multi-kinase inhibitor that inhibits the VEGF receptors VEGFR1, VEGFR2, and VEGFR3 (IC50s = 10, 30, and 47 nM, respectively, in a cell-free enzyme assay).1 It also inhibits PDGFRα, PDGFRβ, and c-Kit (IC50s = 71, 84, and 74 nM, respectively, in a cell-free enzyme assay) as well as additional receptor tyrosine kinases. Pazopanib inhibits upregulation of the surface adhesion proteins ICAM-1 and VCAM-1 induced by VEGF in multiple myeloma cells cocultured with human umbilical vein endothelial cells (HUVECs) and decreases multiple myeloma cell adhesion to HUVECs.2 It also inhibits proliferation of multiple myeloma cells cocultured with HUVECs. Pazopanib (30 and 100 mg/kg) reduces tumor growth, induces apoptosis, decreases angiogenesis, and increases survival in a multiple myeloma mouse xenograft model. Formulations containing pazopanib have been used in the treatment of cancer. | [References]
1. Kumar, R., Knick, V.B., Rudolph, S.K., et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity Mol. Cancer Ther. 6(7),2012-2021(2007).
2. Podar, K., Tonon, G., Satler, M., et al. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma Proc. Natl. Acad. Sci. USA 103(5),19478-19483(2006). |
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