Z-1066 ZSTK474, Free Base, >99%M.W. 417.41 C19H21F2N7O2 [475110-96-4] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 20 mg/mL; soluble in ethanol at 2.5 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 1-5 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •ZSTK474, a novel s-triazine derivative, binds to the ATP-binding site of Class I phosphatidylinositol 3-kinases (PI3K) and inhibits PI3K activity. ZSTK474 has strong antitumor activities against human cancer xenografts (A549, PC-3 and WiDr) when administered orally to mice. Furthermore, ZSTK474 did not show significant toxicity at the doses tested. Yaguchi, S., et al. “Antitumor Activity of ZSTK474, a New Phosphatidylinositol 3-Kinase Inhibitor.” J. Natl. Cancer Inst. 98: 545-556 (2006). •The Class I PI3K inhibitory activity of ZSTK474 is not isoform-specific within the class — it is an ATP-competitive inhibitor of all four Class I PI3K isoforms. However, ZSTK474 inhibits PI3Kδ most potently, with a Ki of 1.8 nM, while it inhibits the α, β and γ isoforms at slightly higher concentrations (6.7 nM, 10.4 nM and 11.7 nM, respectively). Kong, D. and Yamori, T. “ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms.” Cancer Sci. 98: 1638-1642 (2007). •ZSTK474 is a far more potent Class I PI3K inhibitor than LY294002, by a factor of 30-fold or more, and it is far more stable than wortmannin. Kong, D. and Yamori, T., ibid. •ZSTK474 is also less toxic than LY 294002 and wortmannin in animal model tests. Yaguchi, S., et al., op. cit. •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.
