生物活性
WYE-125132 is a highly potent, ATP-competitive and specific mTOR kinase inhibitor with an IC50 of 0.19 nM. WYE-125132 blocked the activity of the both of mTORC1 and mTORC2 in various models of cancer in vitro and in vivo. WYE-125132 is 5,000-fold more selective than PI3Ks. Moreover, WYE-125132 completely blocked amino acid-induced phosphorylation of Maf1, just as S6K1, and 4E-BP1 via the inhibition of mTOR. WYE-132-treated MG63 markedly upregulated the Maf1 amouts in the nucleus. WYE-125132 showed a substantially more effective inhibition in many respects, including cancer cell growth and survival, protein synthesis bioenergetic metabolism, and adaptation to hypoxia by contrast with the rapalog temsirolimus/CCI-779.
化学数据
| 分子量 | 519.6 |
| 分子式 | C27H33N7O4 |
| CAS号 | 1144068-46-1 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO 100 mg/mL |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | WYE-125132 |
| 方法 | Obtaining cell lines of MDA-MB-361, MDA-MB-231, MDA-MB-468, BT549, LNCap, A549, H1975, H157, H460, U87MG, A498, 786-O, HCT116, MG63, Rat1, HEK293, and HeLa from the American Type Culture Collection. Describing cell growth assays and IC50 determination as follows. For tumor cell growth assays, plating cells in 96-well culture plates at 1000 to 3000 cells per well for 24 hours, treating with DMSO or various doses of WYE-125132. Viable cell densities are determined three days later by MTS assay employing an assay kit following the kit assay protocol.Calculating the effect of each treatment as percent of control growth relative to the DMSO-treated cells grown in the same culture plate. Ploting inhibitor dose response curves for determination of IC50 values. |
| 浓度 | 0 to 10 μM |
| 处理时间 | 24 hours |
| 动物实验 |
|---|
| 动物模型 | U87MG, MDA361, H1975, A549, A498, and 786-O cells are injected s.c. into the right flank of CD1 nu/nu mice |
| 配制 | WYE-125132 is dissolved in 5% ethanol, 2% Tween 80, and 5% polyethylene glycol-400 |
| 剂量 | ≤50 mg/kg |
| 给药处理 | Administered via i.v. or p.o. |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9246 mL | 9.6228 mL | 19.2456 mL |
| 5 mM | 0.3849 mL | 1.9246 mL | 3.8491 mL |
| 10 mM | 0.1925 mL | 0.9623 mL | 1.9246 mL |
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