现货大促销,价格低至8折起,量大更优惠,详细咨询客服
全部分类
全部分类
  • WYE-125132 (WYE-132)
WYE-125132 (WYE-132)的可视化放大

WYE-125132 (WYE-132)

Dual mTORC1/mTORC2 inhibitor

原价
¥1787-14312
价格
1430-11450
WYE-125132 (WYE-132)的二维码

所有产品仅用于科学研究,我们不为任何个人用途提供产品和服务

询价有惊喜,量大更优惠 点击这里给我发消息

  • 库存: 现货
可选包装 >>>
首页
  • 货号: ajci13592
  • CAS: 1144068-46-1
  • 别名: N-[4-[1-(1,4-二氧杂螺[4.5]癸烷-8-基)-4-(8-氧杂-3-氮杂双环[3.2.1]辛烷-3-基)-1H-吡唑并[3,4-D]嘧啶-6-基]苯基]-N'-甲基脲,WYE-125132
  • 分子式: C27H33N7O4
  • 分子量: 519.61
  • 纯度: >98%
  • 溶解度: ≥ 13mg/mL in DMSO
  • 储存: Store at -20°C
  • 库存: 现货

Background

WYE-125132 (WYE-132) is highly potent, ATP-competitive, and specific inhibitor of mTOR kinase with IC50 value of 0.19±0.07nmol/L, >5000-fold selective versus PI3Ks [1].


WYE-125132 (WYE-132) has been reported to mTORC1-dependent phosphorylation of S6K (T389) and mTORC2-dependent phos-phorylation of AKT (S473) in immune-complex assay. In addition, in insulin-like growth factor-I(IGF-I)–induced Rat1, the PIK3CA mutant MDA361, or PTEN-null U87MG cells, WYE-125132 (WYE-132) has also been revealed to dose-dependently inhibit P-S6K(T389) and P-AKT(S473) with EC50 in low nanomolar range. Apart from these, WYE-125132 (WYE-132) has shown a potent anti-proliferative agent against MDA361, PC3MM2, U87MG, A549, and HCT116 cell lines. Moreover, WYE-125132 (WYE-132) has noted a stronger inhibition of protein synthesis and cell size in MDA361 and HEK293 cell lines [1].

参考文献:
[1] Yu K1, Shi C, Toral-Barza L, Lucas J, Shor B, Kim JE, Zhang WG, Mahoney R, Gaydos C, Tardio L, Kim SK, Conant R, Curran K, Kaplan J, Verheijen J, Ayral-Kaloustian S, Mansour TS, Abraham RT, Zask A, Gibbons JJ. Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2. Cancer Res. 2010 Jan 15;70(2):621-31. doi: 10.1158/0008-5472.CAN-09-2340. Epub 2010 Jan 12.

Protocol

Cell experiment:

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, HeLa and PC3MM2 are used. MDA361 cells are treated for 3 d with CCI-779 and WYE-132 (0.1 nM, 1 nM, 10 nM,100 nM, 1000 nM 10μM and 100μM). Cell growth assays and IC50 determination are performed. For immunoblotting, cultured cells are treated as indicated. Total cell lysates are prepared using NuPAGE lithium dodecyl sulfate sample buffer and immunoblotted with various antibodies[1].

Animal experiment:

Mice[1] For mTOR biomarker studies, various tumors (400 mm3) grown s.c. in female nude mice are dosed by a single i.v. or oral injection with vehicle or WYE-125132 formulated in 5% ethanol, 2% Tween 80, and 5% polyethylene glycol-400. Tumor lysates are prepared and immunoblotted. For efficacy studies, nude mice bearing U87MG, MDA361, H1975, A549, A498, or 786-O tumors are staged and randomized into treatment groups (n=10). Mice are dosed orally with vehicle or WYE-125132 following qd x5 cycle regimen (5 d on, 2 d off) for up to four cycles. Temsirolimus/CCI-779 is formulated as WYE-132 and dosed i.v. once weekly. Bevacizumab is formulated in PBS and dosed i.p. via its clinical regimen (200 μg/mouse; once weekly). Tumor growth is monitored and analyzed.

参考文献:

[1]. Yu K, et al. Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2.Cancer Res. 2010 Jan 15;70(2):621-631.

动态评分

0.0

没有评分数据
没有评价数据
一键回到顶部
展开 收缩
安捷凯在线客服