ZSTK474

Phosphatidylinositol 3-kinase (PI3K), which is active in signal transduction, generates phosphatidylinositol-3,4,5-tris-phosphate (PIP₃) by phosphorylating phosphatidylinositol-4,5-bisphosphate. PI3K is involved in various cellular processes, including cell survival, vesicle transport, and cytoskeletal rearrangement³. ZSTK474, a novel s-triazine derivative, is an ATP-competitive pan-class I PI3K inhibitor with IC₅₀s of 16 nM, 44 nM, 4.6 nM and 49 nM for PΙ3Κα, PI3Kβ, PI3Kδ and PI3Kγ, respectively⁴. The mean logarithm of GI₅₀ for ZSTK474 was −6.49 at 0.32 μM, which was substantially lower than that observed with LY294002 or wortmannin, indicating that ZSTK474 had stronger cell growth inhibitory activity than either of these two known PI3K inhibitors. At concentration of 1 μM, ZSTK474 reduced the PI3K activity to 4.7% of the untreated control activity. When murine embryonic fibroblast cells were incubated for 15 minutes with 1 μM ZSTK474 before the addition of platelet-derived growth factor, both membrane ruffling and the formation of PIP₃ , a measure of PI3K activity, were blocked. At 10 μM, a higher concentration than its GI₅₀, ZSTK474 induced apoptosis in OVCAR3 cells. When administered orally for 2 weeks, ZSTK474 inhibited the growth of subcutaneously implanted mouse B16F10 melanoma tumors in a dose-dependent manner. Almost complete tumor growth inhibition (i.e., tumor regression) was observed at higher dosages³.

溶解方案(细胞实验)

DMSO 中的溶解度 : 33.33 mg/mL (79.85 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)