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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Design and synthesis of procollagen C-proteinase inhibitors
Eric Turtle1, Nicholas Chow, Charles Yang
1FibroGen Inc., 409 Illinois St, SF, CA 94158, USA.
Bioorganic & Medicinal Chemistry Letters
|November 9, 2012
Abstract:
Non-peptidic inhibitors of procollagen C-proteinase (PCP) were designed from substrate leads. Compounds were optimized for potency and selectivity, with N-substituted aryl sulfonamide hydroxamates having the best combination of these properties. Compounds 89 and 60 have IC(50) values of 10 and 80 nM, respectively, against PCP; excellent selectivity over MMP's 1, 2, and 9; and activity in cell-based collagen deposition assays.
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