Identification of Novel Inhibitors of the Transforming Growth Factor β1 (TGF-β1) Type 1 Receptor (ALK5)
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- 30 January 2002
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 45 (5) , 999-1001
- https://doi.org/10.1021/jm010493y
Abstract
Screening of our internal compound collection for inhibitors of the transforming growth factor β1 (TGF-β1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3,4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-β1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay.Keywords
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