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GW788388

现货
Catalog No.
A8301
ALK5抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 700.00
现货
5mg
¥ 600.00
现货
25mg
¥ 1,800.00
现货
100mg
¥ 3,850.00
现货

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Background

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt425.49
Cas No.452342-67-5
FormulaC25H23N5O2
Solubility≥21.25mg/mL in DMSO, <2.31 mg/mL in EtOH, <2.66 mg/mL in H2O
Chemical NameN-(oxan-4-yl)-4-[4-(5-pyridin-2-yl-1H-pyrazol-4-yl)pyridin-2-yl]benzamide
SDFDownload SDF
Canonical SMILESC1COCCC1NC(=O)C2=CC=C(C=C2)C3=NC=CC(=C3)C4=C(NN=C4)C5=CC=CC=N5
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

NmuMG和MDA-MD-231细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

1、2.5、5或10 μM;1小时

实验结果

在NmuMG和MDA-MD-231细胞中,GW788388呈剂量依赖性地抑制TGF-β诱导的Smad2磷酸化。此外,GW788388也抑制TGF-β介导的Smad1/5磷酸化(需要ALK5和TbRII)。

动物实验 [1]:

动物模型

自发性糖尿病肾病db/db小鼠模型

给药剂量

2 mg/kg/day;口服给药;持续5周

实验结果

在自发性糖尿病肾病db/db小鼠模型中,GW788388显着减少胶原沉积,大大改善肾小球病(其特征包括肾小球系膜基质扩张、肾小球系膜肥厚、增殖和肾小球基底膜增厚),以及降低尿白蛋白浓度。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

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.

生物活性

描述 GW788388是一种有效的和选择性的ALK5抑制剂,IC50值为18 nM。
靶点 ALK5          
IC50 18 nM          

质量控制

化学结构

GW788388