您好,欢迎来到试剂仪器网! [登录] [免费注册]
试剂仪器网
位置:首页 > 产品库 > GW788388
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:
 
GW788388
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。
GW788388图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
5mg电议
25mg电议
100mg电议

产品介绍
GW788388 是一种有效的选择性 ALK5 抑制剂,IC50 为 18 nM,还抑制 TGF-β II 型受体和激活素 II 型受体的活性,而不抑制 BMP II 型受体。

Cell lines

NMuMG and MDA-MD-231 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 ℃ for several months.

Reaction Conditions

1, 2.5, 5 or 10 μM; 1 hr

Applications

In NMuMG and MDA-MD-231 cells, GW788388 dose-dependently inhibited TGF-β-induced Smad2 phosphorylation. In addition, TGF-β-mediated Smad1/5 phosphorylation, which requires ALK5 and TbRII, was also inhibited by GW788388.

Animal models

A db/db mouse model of spontaneous diabetic nephropathy

Dosage form

2 mg/kg/day; p.o.; for 5 weeks

Applications

In a db/db mouse model of spontaneous diabetic nephropathy, GW788388 significantly reduced collagen deposits, substantially improved glomerulopathy (marked by mesangial matrix expansion, mesangial hypertrophy, proliferation, and glomerular basement membrane thickening), as well as decreased urinary albumin concentrations.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

产品描述

GW788388 is a selective inhibitor of ALK5 with IC50 value of 18 nM [1].

Transforming growth factor beta (TGF-beta) type I receptor (ALK5) is the receptor of TGF-beta and plays an important role in transducing the TGF-beta signal from the cell surface to the cytoplasm [2 ].

GW788388 is a potent TGF-beta type I receptor inhibitor and has a much improved pharmacokinetic profile compared with the reported TGF-beta type I receptor inhibitor SB431542. When tested with human embryonic kidney 293T cells transfected with ALK5, TβRII, BMPRII or ActRII, GW788388 exhibited specific inhibitory function on the autophosphorylation of ALK5 and TβRII, while had some extent to ActRII and had no effect on BMPRII. Further, using Namrumurine mammary gland (NMuMG), MDA-MB-231, renal cell carcinoma (RCC)4 and U2OS cell lines, GW788388 treatment inhibited TGF-β-induced Smad2 phosphorylation, inhibited TGF-β-induced EMT and growth, and TGF-β-induced fibrotic responses [1]. In ESCC/fibroblast/HMVEC co-culture model, GW788388 treatment (1 μM) resulted in a complete reversal of vascular network formation that indicated GW788388 blocked ESCC-induced neoangiogenesis [3].

In 6-month-old db/db mouse model of spontaneous diabetic nephropathy, administration of GW788388 at the dose of 2 mg/kg/day orally for 5 weeks attenuated renal fibrosis without any side-effect [1]. In 10-week Sprague-Dawley rats model, oral administration of GW788388 (100-1000 mg/kg/day) for 4 days induced the thickness of femoral physis in a dose-dependent manner and severity of physeal changes , as well as subphyseal hyperostosis, increased with duration of dosing progressing from minimal to moderate in rats given 300 mg/kg/day for 10 days [2].

References:
[1].  Petersen, M., et al., Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int, 2008. 73(6): p. 705-15.
[2].  Frazier, K., et al., Inhibition of ALK5 signaling induces physeal dysplasia in rats. Toxicol Pathol, 2007. 35(2): p. 284-95.
[3].  Noma, K., et al., The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis. Gastroenterology, 2008. 134(7): p. 1981-93.