Imatinib as a novel therapeutic approach for fibrotic disorders.

Imatinib mesylate is a small molecule that binds to the ATPbinding pocket of Abelson kinase (c-Abl) and blocks efficiently its tyrosine kinase activity. c-Abl is an important downstream signalling molecule of TGF[1]. The importance of c-Abl for the pro-fibrotic effects of TGFis emphasized by the observation that the induction of extracellular matrix proteins by TGFis strongly decreased in cells deficient for c-Abl. In addition to its effects on c-Abl, imatinib blocks the tyrosine kinase activity of PDGF receptors. Thus, imatinib targets simultaneously and also rather selectively TGFand PDGF signalling, two major pro-fibrotic pathways in SSc [2].