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Updated: Jul 18, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Potent, selective pyrone-based inhibitors of stromelysin-1
David T Puerta1, John Mongan, Ba L Tran
1Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, and Center for Theoretical Biological Physics, University of California-San Diego, La Jolla, CA 92093, USA.
Abstract:
In an effort to develop alternatives to hydroxamate-based matrix metalloproteinase inhibitors (MPIs), we have utilized the drug discovery program LUDI enhanced with the structural coordinates of a bioinorganic model complex. This method has yielded the first pyrone-based MPIs. The inhibitors demonstrate nanomolar potency against MMP-3 and are selective for MMP-3 over MMP-2 and MMP-1. We postulate that the potency and unusual selectivity profile of these MPI is attributable to the pyrone chelating group.
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