ZSTK474 (475110-96-4) is a novel Class I phosphatidylinositol 3-kinase (PI3K) inhibitor. ZSTK474 is an ATP-competitive inhibitor of all four Class I PI3K isoforms. However, it inhibits PI3Kδ most potently, with a Ki of 1.8 nM, while inhibiting the α, β and γ isoforms at slightly higher concentrations (6.7 nM, 10.4 nM and 11.7 nM, respectively)1. Displays potent antitumor activity against human cancer xenografts (A549, PC-3 and WiDr) when administered to mice2. ZSTK474 displays potent anti-inflammatory activity via modulation of human CD14+ monocyte-derived dendritic cell functions and suppresses experimental autoimmune encephalomyelitis3. Ameliorates the progression of adjuvant-induced arthritis in a rat model4.
1) Kong and Yamori et al. (2007), ZSTK474 is an ATP-competative inhibitor of class I phosphatidylinositol 3 kinase isoforms; Cancer Sci., 98 1638
2) Yaguchi et al. (2006), Antitumor activity of ZST474, a new phosphatidylinositol 3-kinase inhibitor; J. Natl. Cancer Inst., 98 545
3) Xue et al. (2014), ZSTK474, a novel PI3K inhibitor, modulates human CD14+ monocyte-derived dendritic cell functions and suppresses experimental autoimmune encephalomyelitis; J. Mol. Med. (Berl.), 92 1057
4) Haruta et al. (2012), Inhibitory effects of ZST474, a phosphatidylinositol 3-kinase inhibitor, on adjuvant-induced arthritis in rats; Inflamm. Res., 61 551