| 产品描述： | WYE-687 is an ATP-competitive mTOR inhibitor with an IC50 of 7 nM. WYE-687 concurrently inhibits activation of mTORC1 and mTORC2. WYE-687 also inhibits PI3Kα and PI3Kγ with IC50s of 81 nM and 3.11 μM, respectively. |
| 靶点： |
PI3K alpha:81 nM (IC50);PI3K gamma:3.11 μM (IC50);mTORC1;mTORC2;mTOR:7 nM (IC50);CK1 gamma1:17.8 μM (IC50);p38 alpha:28.9 μM (IC50) |
| 体外研究： |
In the DELFIA measuring His6-S6K1 T389 phosphorylation, WYE-687 inhibits recombinant mTOR enzyme with an IC50 of 7 nM. HL-60 AML cells are treated with applied concentrations of WYE-687 (33-1000 nM), MTT cell survival assay results demonstrate that WYE-687 potently inhibits HL-60 cell survival in a dose-dependent manner. A time dependent response by WYE-687 is also noticed. The number of dead (“trypan blue” positive) HL-60 cells is significantly increased following applied WYE-687 (100-1000 nM) treatment. At the meantime, HL-60 cell proliferation, tested by [H3] Thymidine integration assay, is also inhibited by the WYE-687. Results show that WYE-687 is also antisurvival (“cytotoxic”) to the other AML cell lines: U937, THP-1 and AML-193 |
| 体内研究： |
U937 cells are inoculated into the flanks of SCID/beige mice. When xenografted tumors reach a volume around 100 mm3, mice are orally administrated with either vehicle control (5% ethanol, 2% Tween 80, and 5% polyethylene glycol-400) or WYE-687 (5 or 25 mg/kg) daily for a total of 7 days. The WYE-687 regimen utilized in this study is based on preexperimental results and related studies. WYE-687 administration (5 or 25 mg/kg, daily) significantly inhibits U937 xenograft tumor growth in SCID mice, and the in vivo activity by WYE-687 is dose-dependent. At day 15, the 5 mg/kg WYE-687-treated tumors and 25 mg/kg WYE-687-treated tumors are 50% and 75% smaller than the vehicle control tumors, respectively. Tumor weights of WYE-687-treated mice are also significantly lower than that of vehicle group. Oral administration of WYE-687 potently inhibits U937 leukemic xenograft tumor growth in SCID mice, without causing significant toxicities |
| 细胞实验： |
For cell cycle analysis, cells are seeded in 96-well culture plates at 10,000 cells per well for 24 hours, treated with various inhibitors for 24 hours or 48 hours. Following treatment, cells are harvested, washed with PBS and fixed overnight at -20 °C in 70% ethanol. Cells are washed, stained with propidium iodide and analyzed for cell cycle profile (acquired 5000 cells/well) on Guava PCA-96 instrument according to the Guava Cell Cycle Protocol(Only for Reference) |
| 参考文献： |
1. Yu K, et al. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res. 2009 Aug 1;69(15):6232-40. 2. Cheng F, et al. Preclinical evaluation of WYE-687, a mTOR kinase inhibitor, as a potential anti-acute myeloid leukemia agent. Biochem Biophys Res Commun. 2016 Feb 5;470(2):324-330. |
| 溶解性： |
soluble in DMSO |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.892 ml |
9.459 ml |
18.918 ml |
| 5 mM |
0.378 ml |
1.892 ml |
3.784 ml |
| 10 mM |
0.189 ml |
0.946 ml |
1.892 ml |
| 50 mM |
0.038 ml |
0.189 ml |
0.378 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
