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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-2878

Akhmetshina, A; Dees, C; Pileckyte, M; Maurer, B; Axmann, R; Jüngel, A; Zwerina, J; Gay, S; Schett, G; Distler, O; Distler, J H W (2008). Dual inhibition of c-abl and PDGF receptor signaling by dasatinib and nilotinib for the treatment of dermal fibrosis. FASEB Journal, 22(7):2214-2222.

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Abelson kinase (c-abl) and platelet-derived growth factor (PDGF) are key players in the pathogenesis of systemic sclerosis (SSc). The aim of the present study was to evaluate the antifibrotic potential of dasatinib and nilotinib, 2 novel inhibitors of c-abl and PDGF, which are well tolerated and have recently been approved. Dasatinib and nilotinib dose-dependently reduced the mRNA and protein levels of extracellular matrix proteins in human stimulated dermal fibroblasts from SSc patients (IC(50) of 0.5-2.0 nM for dasatinib and 0.8-2.5 nM for nilotinib). In a mouse model of bleomycin-induced dermal fibrosis, dasatinib and nilotinib potently reduced the dermal thickness, the number of myofibroblasts, and the collagen content of the skin in a dose-dependent manner at well-tolerated doses. These data indicate that dasatinib and nilotinib potently inhibit the synthesis of extracellular matrix in vitro and in vivo at biologically relevant concentrations. Thus, we provide the first evidence that dasatinib and nilotinib might be promising drugs for the treatment of patients with SSc.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:25 Aug 2008 13:31
Last Modified:05 Apr 2016 12:25
Publisher:Federation of American Societies for Experimental Biology
Publisher DOI:10.1096/fj.07-105627
Official URL:http://www.fasebj.org/cgi/reprint/22/7/2214
PubMed ID:18326784

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