ZSTK474 BASE
ZSTK474
CAS: 475110-96-4
Molecular Formula: C19H21F2N7O2
ZSTK474 BASE - Names and Identifiers
ZSTK474 BASE - Physico-chemical Properties
| Molecular Formula | C19H21F2N7O2 |
| Molar Mass | 417.41 |
| Density | 1.57 |
| Melting Point | 217-219 °C(Solv: ethanol (64-17-5)) |
| Boling Point | 640.3±65.0 °C(Predicted) |
| Solubility | Soluble in DMSO (up to 20 mg/ml) or in Ethanol (up to 2.5 mg/ml with warming). |
| Appearance | White powder. |
| Color | White or off-white |
| pKa | 5.21±0.10(Predicted) |
| Storage Condition | -20°C |
| Stability | Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months. |
| Use | ZSTK474 can inhibit type I PI3K subtype, IC50 is 37 nM, and has the most significant effect on PI3Kδ. |
| In vitro study | At a concentration of 1 μm, ZSTK474 was effective in reducing PI3K activity to 4.7% of the control level, whereas LY2194002 only reduced its activity to 44.6% of the control. ZSTK474 inhibits recombinant p110β,-γ, and-δ activity with IC50 of 17 nM,53 nM, and 6 nM, respectively. ZSTK474 exhibited potent anti-proliferative activity against a panel of 39 human carcinoid cell lines, with an average GI50 of 0.32 μm, LY294002 and wortmannin were more potent than average GI50 of 7.4 μm and 10 μm, respectively. 1 μm ZSTK474 treatment blocked platelet-derived growth factor-induced cell membrane edge wave motion and PIP3 production in mouse embryonic fibroblasts (MEFs). 10 μm ZSTK474 induced OVCAR3 cell apoptosis and induced complete G1 phase arrest of cell cycle, but did not cause A549 cell apoptosis. 0.5 μm ZSTK474 treatment significantly reduced phosphorylated Akt and GSK-3β levels, as well as expression of cyclin D1 protein. ZSTK474 also dose-dependently inhibited the phosphorylation of other downstream signaling components involved in the regulation of cell proliferation, including FKHRL1,FKHR,TSC-2,mTOR, and p70S6K. ZSTK474 did not inhibit mTOR at 0.1 μm, and even at a concentration of 100 μm, ZSTK474 only inhibited mTOR activity by less than 40%. ZSTK474 blocked VEGF-induced cell migration and tube formation in human umbilical vein endothelial cells (HUVECs) and inhibited HIF-1α expression and VEGF secretion in RXF-631L of cells, showing potent in vitro anti-angiogenic activity. ZSTK474 treatment inhibits the production of IFNγ and IL-17 in T cells activated by concanavalin A and inhibits proliferation and PGE(2) production by fibroblast-like synoviocytes (FLS). |
| In vivo study | Oral administration of ZSTK474 dose-dependently inhibited the growth of B16F10 Melanoma in mice implanted subcutaneously on day 14, resulting in 100,200, 400, or 28.5% mg/kg doses, respectively, or 4.9% tumor regression, superior to the other four major anticancer drugs irinotecan,cisplatin,doxorubicin, and 5-fluorouracil, with respective maximum tolerated doses for tumor regression of 96%,35.7%,24%, or 68.3%. ZSTK474 treatment at 400 mg/kg completely inhibited the growth of A549,PC-3, and WiDr in mice and induced the regression of A549 xenografts. ZSTK474 significantly inhibited tumor growth in the RXF-631L xenograft model, consistent with a significant reduction in the number of microvessels in ZSTK474 treated mice. Oral administration of ZSTK474 ameliorates the development of adjuvant arthritis in rats. |
ZSTK474 BASE - Risk and Safety
| HS Code | 29349990 |
ZSTK474 BASE - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.396 ml | 11.978 ml | 23.957 ml |
| 5 mM | 0.479 ml | 2.396 ml | 4.791 ml |
| 10 mM | 0.24 ml | 1.198 ml | 2.396 ml |
| 5 mM | 0.048 ml | 0.24 ml | 0.479 ml |
Last Update：2024-01-02 23:10:35
ZSTK474 BASE - Reference Information
| biological activity | ZSTK474 inhibits type I PI3K subtype. in cell-free test, IC50 is 37 nM, which has the most significant effect on PI3Kδ. Phase 1/2. |
| target | TargetValue PI3Kδ (Cell-free say) 4.6 nM PI3Kα (Cell-free say) 16 nM PI3K (Cell-free say) 37 nM PI3Kβ (Cell-free say) 44 nM PI3Kγ (Cell-free say) 49 nM |
| Target | Value |
| PI3Kδ (Cell-free assay) | 4.6 nM |
| PI3Kα (Cell-free assay) | 16 nM |
| PI3K (Cell-free assay) | 37 nM |
| PI3Kβ (Cell-free assay) | 44 nM |
| PI3Kγ (Cell-free assay) | 49 nM |
| in vitro study | ZSTK474 effectively reduced PI3K activity to 4.7% of the control group level at a concentration of 1 μM, while the LY2194002 only reduced its activity to 44.6% of the control group. ZSTK474 inhibited recombinant p110β,-γ, and-δ activities with IC50 of 17 nM,53 nM, and 6 nM, respectively. ZSTK474 showed effective antiproliferative activity against a group of 39 human carcinoid cell lines with an average GI50 of 0.32 μM, which was more effective than LY294002 and wortmannin with an average GI50 of 7.4 μM and 10 μM, respectively. 1 μM ZSTK474 therapy blocked platelet-derived growth factor-induced membrane marginal wave and PIP3 production in mouse embryonic fibroblasts (MEFs). 10 μM ZSTK474 induced apoptosis of OVCAR3 cells and induced complete G1 phase arrest of cell cycle, but did not cause apoptosis of A549 cells. 0.5 μM ZSTK474 treatment significantly reduced phosphorylated Akt and GSK-3β levels and cyclin D1 protein expression. ZSTK474 also dose-dependently inhibits phosphorylation of other downstream signaling components involved in cell proliferation regulation, including FKHRL1,FKHR,TSC-2,mTOR, and p70S6K. ZSTK474 did not inhibit mTOR at 0.1 μM, even at 100 μM concentration, ZSTK474 only inhibited less than 40% of mTOR activity. ZSTK474 blocked VEGF-induced cell migration and lumen formation in human umbilical vein endothelial cells (HUVECs), and inhibited HIF-1α expression and VEGF secretion in RXF-631L cells, showing effective anti-angiogenic activity in vitro. ZSTK474 treatment inhibited IFNγ and IL-17 production in concanavalin A- activated T cells, and inhibited proliferation and PGE(2) production by fibroblast-like synovial cells (FLS). |
| in vivo study | ZSTK474 oral administration, dose-dependent inhibition of subcutaneous implanted mice B16F10 melanoma growth, at the dose of 100,200, or 400 mg/kg on the 14th day, 28.5%,7.1%, or 4.9% tumor regression is produced, respectively, the effect is better than that of the other four main anticancer drugs, irinotecan,cisplatin,doxorubicin, and 5-fluorouracil, which have their respective maximum tolerated doses of 96%,35.7%,24%, or 68.3% for tumor regression. 400 mg/kg ZSTK474 therapy completely inhibited the growth of A549,PC-3, and WiDr in mice and induced regression of A549 transplanted tumor. ZSTK474 significantly inhibited tumor growth in RXF-631L xenograft models, consistent with a significant reduction in the number of microvasculature in ZSTK474-treated mice. In rats, ZSTK474 oral administration improves the development of adjuvant arthritis. |
Last Update：2024-04-09 20:45:29
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CAS: 475110-96-4
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CAS: 475110-96-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
Product Name: ZSTK474 Visit Supplier Webpage Request for quotation
CAS: 475110-96-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 475110-96-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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