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 > SAR405
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:
 
SAR405
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。
SAR405图片
CAS NO:1523406-39-4
规格:98%
分子量:443.85
包装与价格:
包装价格(元)
2mg电议
5mg电议
10mg电议
25mg电议

产品介绍
Selective ATP-competitive inhibitor of Vps34
CAS:1523406-39-4
分子式:C19H21ClF3N5O2
分子量:443.85
纯度:98%
存储:Store at -20°C

Background:

SAR405 is a selective ATP-competitive inhibitor of Vps34 with a Kd value of 1.5 nM.
Vps34 is a phosphoinositide 3-kinase (PI3K) class III isoform that plays important role in autophagy. Vps34 was originally described in yeast to be involved in vesicle trafficking. SAR405 is a first-in-class catalytic Vps34 inhibitor and represents a unique pharmacological tool to investigate the biology around this protein. This compound has an exquisite protein and lipid kinase selectivity profile that is explained by its unique binding mode and molecular interactions within the ATP binding cleft of human Vps34. This is the first potent and specific Vps34 inhibitor described so far. Inhibition of Vps34 kinase activity by SAR405 affects both late endosome-lysosome compartments and prevents autophagy.
Using SAR405, inhibition of Vps34 did not affect early events of endocytosis but resulted in an accumulation of swollen late endosome-lysosomes. A defect of cathepsin D maturation was also identified upon treatment with SAR405, indicating that the function of lysosomes is impaired. This result is in agreement with a previous report using Vps34 siRNA, which affects vesicle trafficking from late endosomes to lysosomes.
SAR405 had an IC50 of 1 nM in the phosphorylation of a PtdIns substrate by human recombinant Vps34 enzyme. This relocalization of the GFP-FYVE indicated that SAR405 inhibits PtdIns3P formation. As SAR405 was found to not be active up to 10 μM on class I and class II PI3Ks as well as on mTOR. Binding of SAR405 to the ATP site of protein and lipid kinases from the lysate of Jurkat cells was measured after incubation at 1μM, which is more than 600-fold the KD for recombinant Vps34. SAR405 did not affect the Akt phosphorylation in the PC3 cell line at concentrations up to 10 μM.
参考文献:
[1]. Ronan B, Flamand O1, Vescovi L et al. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014 Dec;10(12):1013-9.