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P-6706 Pazopanib, Free Base, >99%

[GW-786034] [Armala]

M.W. 437.52

C21H23N7O2S

[444731-52-6]

Storage:  Store at or below -20 ºC.  Solubility:  Soluble in DMSO at 8.3 mg/mL with slight warming; very poorly soluble in ethanol; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility.  Disposal:  A

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• Pazopanib is an oral, second-generation, potent and selective multi-targeted tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor and c-kit, key proteins responsible for tumor growth and angiogenesis.  Pazopanib showed good potency against all of the human VEGFRs and some related tyrosine receptor kinases in vitro, and demonstrated antitumor activity against renal cell carcinoma (RCC), and breast, lung, and other related cancers.  Sloan, B. and Scheinfeld, N.S.  "Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy."  Curr. Opin. Investig. Drugs 9:  1324-1335 (2008).

• Preclinical evaluation has demonstrated excellent anti-tumor and anti-angiogenic activity.  A Phase II clinical trial of pazopanib in untreated or cytokine/bevacizumab pretreated renal cell carcinoma has revealed promising activity with a favorable toxicity profile.  Sonpavde, G., et al.  "Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma."  Expert Opin. Investig. Drugs 17:  253-261 (2008).

• Orally administered Pazopanib has good bioavailability to the retina/choroid and strongly suppresses choroidal neovascularization (CNV) in a dose-dependent manner in mice.  Takahashi, K., et al.  "Suppression and regression of choroidal neovascularization by the multitargeted kinase inhibitor pazopanib."  Arch. Ophthalmol. 127:  494-499 (2009).

• Pazopanib inhibits in vivo tumor cell growth in a mouse xenograft model of human multiple myeloma (MM) associated with increased MM cell apoptosis, prolonged survival, and decreased angiogenesis.  Podar, K., 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:  19478-19483 (2006).

• Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use.

• This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.

• Not available in some countries; not available to some institutions; not available for some uses.