Inhibition of ALK5 as a new approach to treat liver fibrotic diseases

被引：27

作者：

de Gouville, Anne-Charlotte ^{[1
]}

Huet, Stephane ^{[1
]}

机构：

[1] Glaxo SmithKline Pharmaceut, Dept Biol, F-91951 Les Ulis, France

来源：

DRUG NEWS & PERSPECTIVES | 2006年 / 19卷 / 02期

关键词：

D O I：

10.1358/dnp.2006.19.2.977444

中图分类号：

R9 [药学];

学科分类号：

1007 [药学];

摘要：

Liver fibrosis is the result of an unbalanced wound healing response to a chronic hepatic injury. Transforming growth factor-beta (TGF-beta) plays a major role in this process via the activation of hepatic stellate cells. Various approaches have been tested in animal models of fibrosis to block the effects of TGF-beta, including antibodies and soluble receptors. Here, we discuss the potential use of TGF-beta signaling inhibitors, acting at the TGF-beta type I receptor kinase (ALK5) level, as a possible therapy for liver fibrosis. Thus far, there is only one ALK5 inhibitor (GW6604) for which activity in models of liver fibrosis has been described, showing clear antifibrotic effects resulting in liver function improvement. However, due to the pleiotropic effects of TGF-beta, the beneficial antifibrotic effects of ALK5 inhibition should be carefully balanced against the potential risk of unwanted effects stemming from chronic treatment. (C) 2006 Prous Science. All rights reserved.

引用

页码：85 / 90

页数：6

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