Abstract |
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.
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Authors | Anne-Charlotte de Gouville, Stephane Huet |
Journal | Drug news & perspectives
(Drug News Perspect)
Vol. 19
Issue 2
Pg. 85-90
(Mar 2006)
ISSN: 0214-0934 [Print] United States |
PMID | 16628263
(Publication Type: Journal Article, Review)
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Copyright | Copyright 2006 Prous Science |
Chemical References |
- 2-phenyl-4-(3-pyridin-2-yl-1H-pyrazol-4-yl)pyridine
- Pyrazoles
- Pyridines
- Receptors, Transforming Growth Factor beta
- Transforming Growth Factor beta
- Protein Serine-Threonine Kinases
- Activin Receptors, Type I
- Receptor, Transforming Growth Factor-beta Type I
- TGFBR1 protein, human
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Topics |
- Activin Receptors, Type I
(antagonists & inhibitors)
- Animals
- Disease Models, Animal
- Humans
- Liver Cirrhosis
(drug therapy, pathology)
- Protein Serine-Threonine Kinases
- Pyrazoles
(adverse effects, pharmacology, therapeutic use)
- Pyridines
(adverse effects, pharmacology, therapeutic use)
- Receptor, Transforming Growth Factor-beta Type I
- Receptors, Transforming Growth Factor beta
(antagonists & inhibitors)
- Transforming Growth Factor beta
(physiology)
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