WYE-354 是一种 ATP 竞争性的 mTOR 抑制剂，

WYE-354

WYE-354 是一种 ATP 竞争性的 mTOR 抑制剂，IC₅₀ 为 5 nM。WYE-354 也抑制 PI3Kα 和 PI3Kγ，IC₅₀ 分别为 1.89 μM 和 7.37 μM。WYE-354 抑制 mTORC1和 mTORC2。WYE-354 在体外能诱导自噬 (autophagy) 激活.

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。从产品的HNMR数据解析到生物活性数据，从客户的询价到产品的售后服务，我们拥有着完善的管理体系，从而保证我们的服务更加高效、准确。努力为中国的医药行业发展注入新的活力，我们将成为您研发工作值得信赖的伙伴。

生物活性    
WYE-354 is an ATP-competitive mTOR inhibitor with an IC50 of 5 nM. WYE-354 also inhibits PI3Kα and PI3Kγ with IC50s of 1.89 μM and 7.37 μM, respectively. WYE-354 inhibits both mTORC1 and mTORC2. WYE-354 induces autophagy activation in vitro[3].

体外研究(In Vitro)    
In the DELFIA measuring His6-S6K1 T389 phosphorylation, WYE-354 inhibits recombinant mTOR enzyme with an IC50 of 5 nM[1]. Cell viability is analyzed by MTS assay. G-415 and TGBC-2TKB cell lines are treated with increasing concentrations of WYE-354 (0.1, 1, 5 and 10 μM) for 24, 48, and 72 hours. WYE-354 significantly reduces cell viability starting at a 1 μM concentration after a 24 hours exposure, in both studied cell lines (P<0.001). A decrease in cell viability is not observed at a dose of 100 nM, except for the TGBC-2TKB cell line after 72 hours of treatment[2].

体内研究(In Vivo)    
The effect of Rapamycin and WYE-354 on tumor growth is evaluated in xenograft GBC tumor models. 2×106 or 5×106 cells of G-415 or TGBC2TKB, respectively, are xenotransplanted into NOD-SCID mice subcutaneously. When tumors reach an average volume of 100 mm3, the mice are treated either with Rapamycin or WYE354. Rapamycin is administered i.p. at a concentration of 10 mg/kg, daily for 5 days per week for 3 weeks, while WYE-354 is administrated at a daily i.p. dose of 50 mg/kg for 5 days. Mice are sacrificed 30 days after the initiation of the treatments and an autopsy is performed that include removal of the entire tumor area. Mice treated with WYE-354 exhibit 68.6% and 52.4% reduction in average tumor size (P<0.01; P<0.01), as well as 82.9% and 45.5% (P<0.01; ns) reduction in tumor weight, respectively[2].
分子量    
495.53

性状    
Solid

Formula    
C24H29N7O5

CAS 号    
1062169-56-5

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : 6.67 mg/mL (13.46 mM; Need ultrasonic)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.0180 mL    10.0902 mL    20.1804 mL
5 mM    0.4036 mL    2.0180 mL    4.0361 mL
10 mM    0.2018 mL    1.0090 mL    2.0180 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 0.67 mg/mL (1.35 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: ≥ 0.67 mg/mL (1.35 mM); Clear solution

3.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 0.67 mg/mL (1.35 mM); Clear solution
 

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.  [Content Brief] [2]. Weber H, et al. Rapamycin and WYE-354 suppress human gallbladder cancer xenografts in mice. Oncotarget. 2015 Oct 13;6(31):31877-88. [Content Brief] [3]. Lijun Wang, et al. Autophagy inhibition sensitizes WYE-354-induced anti-colon cancer activity in vitro and in vivo. Tumour Biol. 2016 Sep;37(9):11743-11752.  [Content Brief]