V-8303 Vatalanib, Dihydrochloride Salt, >99% [CGP-79787] [PTK 787] [ZK222584] M.W. 419.73 C20H15ClN4•2HCl [212141-51-0] M.I. 14: 9939 Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 10-20 mg/mL with warming; very poorly soluble in ethanol; soluble in water at 100 mg/mL; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •Vatalanib is a potent, selective, orally active inhibitor of the VEGFR tyrosine kinases VEGFR-1 (Flt-1, IC50 = 77 nM) and VEGFR-2 (FLK-1/KDR, IC50 = 37 nM), with slightly higher potency against the latter. At higher concentrations, other tyrosine kinases are also inhibited, including PDGFR-β (IC50 = 580 nM), c-KIT (IC50 = 730 nM), FLT-4 (IC50 = 660 nM) and c-FMS (IC50 = 1.4 µM). On the other hand, vatalanib is not active against the EGFR, c-SRC, v-ABL, and protein kinase Cα (IC50 > 10 µM). Wood, J.M., et al. “PTK787/ZK 222584, a Novel and Potent Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, Impairs Vascular Endothelial Growth Factor-induced Responses and Tumor Growth after Oral Administration.” Cancer Res. 60: 2178-2189 (2000). •Vatalanib dose-dependently inhibits proliferation of MM cells and patient cells (IC50 = 1-5 µM), which are both sensitive and resistant to conventional therapy. Vatalanib increases the inhibitory effect of dexamethasone on growth of MM cells and can decrease the protective effect of interleukin 6 (IL-6) against dexamethasone-induced apoptosis. Vatalanib (1 µM) also inhibits VEGF-induced migration of MM cells across an extracellular matrix. Importantly, vatalanib also blocks the increased MM cell proliferation and increased IL-6 and VEGF secretion in cultures of MM cells adherent to bone marrow stem cells. Lin, B., et al. “The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment.” Cancer Res. 62: 5019-5026 (2002). •Vatalanib inhibited VEGF-induced phosphorylation (IC50’s of 17 nM and 34 nM for HUVECs and CHO cells, respectively), blocked thymidine incorporation induced by VEGF in HUVECs (IC50 = 7.1 nM), prevented VEGF-induced HUVEC migration dose dependently (IC50 = 58 nM), and inhibited tumor cell proliferation with an IC50 of 17 µM and 18 µM for A431 and DU145 cells, respectively and sprout formation in rat aortas (IC50 = 675 nM). Wood, J.M., et al. “PTK787/ZK 222584, a Novel and Potent Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, Impairs Vascular Endothelial Growth Factor-induced Responses and Tumor Growth after Oral Administration.” Cancer Res. 60: 2178-2189 (2000). •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.
