WYE-687

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

WYE-687 是一种 ATP 竞争性选择性 mTOR 抑制剂，IC50 为 7 nM；阻断 mTORC1/pS6K(T389) 和 mTORC2/P-AKT(S473)，但未观察到对 P-AKT(T308) 的影响。

WYE-687 is a potent and ATP-competitive and selective inhibitor of mTOR with IC50 of 7 nM.

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.

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.

WYE687 | WYE 687 | WYE-687

Others

Other Targets

mTOR , PI3Kα , PI3Kγ , p38α , Src

Cancer

——

1062161-90-3

528.61

C28H32N8O3

>98% (HPLC)

In Vitro:?DMSO : 25 mg/mL (47.29 mM)

COC(=O)NC1=CC=C(C=C1)C2=NC3=C(C=NN3C4CCN(CC4)CC5=CN=CC=C5)C(=N2)N6CCOCC6

methyl (4-(4-morpholino-1-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)carbamate

(-20℃)

With Ice Pack

≥ 2 years