您好,欢迎来到化工原料网! [登录] [免费注册]
化工原料网
位置:首页 > 产品库 > GNE-477
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
GNE-477
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GNE-477图片
CAS NO:1032754-81-6
规格:98%
分子量:504.63
包装与价格:
包装价格(元)
1mg电议
5mg电议

产品介绍
dual PI3K/mTOR inhibitor
CAS:1032754-81-6
分子式:C21H28N8O3S2
分子量:504.63
纯度:98%
存储:Store at -20°C

Background:

IC50: 4 and 21 nmol/L for PI3K and mTOR, respectively


GNE-477 is a potent dual PI3K/mTOR inhibitor. Owing to the common association with oncogenic malignancies, the PI3K/AKT/mTOR signaling pathway is regarded as an attractive area of research for the identification of oral small molecule inhibitors.


In vitro: GNE-477 was found to inhibit PI3K-α, β, δ, and γ with IC50s of 4, 86, 6, and 15 nM, respectively. [1].


In vivo: A direct comparison of GNE-477 with its des-methyl analog revealed that the trend of reduced in vivo clearance in rats is also observed in dogs and mice. The clearance improvement was significant in dogs where the des-methyl analog was cleared at two-thirds the rate of hepatic blood flow while GNE-477 had low clearance. In an study evaluating the tumor growth inhibition of a PC3 tumor xenograft10 over 14 days, stasis was achieved at a 20 mg/kg QD dose of GNE-477 and significant inhibition was found with doses as low as 1 mg/kg QD. GNE-477 was generally well tolerated during this study as shown by acceptable levels of weight loss comparable to that in the vehicle cohort [1].


Clinical trial: N/A


Reference:
[1] Heffron TP,Berry M,Castanedo G,Chang C,Chuckowree I,Dotson J,Folkes A,Gunzner J,Lesnick JD,Lewis C,Mathieu S,Nonomiya J,Olivero A,Pang J,Peterson D,Salphati L,Sampath D,Sideris S,Sutherlin DP,Tsui V,Wan NC,Wang S,Wong S,Zhu BY.  Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor. Bioorg Med Chem Lett.2010 Apr 15;20(8):2408-11.