Development of a Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-7/-13 Inhibitor

Matrix metalloproteinase 7 (MMP-7) is a member of the MMP superfamily and is able to degrade extracellular matrix proteins such as casein, gelatin, fibronectin and proteoglycan. MMP-7 is a validated target for the development of small molecule drugs against cancer. MMP-13 is within the enzyme class...

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Detalles Bibliográficos
Autores principales: Fischer, Thomas, Riedl, Rainer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151531/
https://www.ncbi.nlm.nih.gov/pubmed/32961647
http://dx.doi.org/10.3390/molecules22091548
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author Fischer, Thomas
Riedl, Rainer
author_facet Fischer, Thomas
Riedl, Rainer
author_sort Fischer, Thomas
collection PubMed
description Matrix metalloproteinase 7 (MMP-7) is a member of the MMP superfamily and is able to degrade extracellular matrix proteins such as casein, gelatin, fibronectin and proteoglycan. MMP-7 is a validated target for the development of small molecule drugs against cancer. MMP-13 is within the enzyme class the most efficient contributor to type II collagen degeneration and is a validated target in arthritis and cancer. We have developed the dual MMP-7/-13 inhibitor ZHAWOC6941 with IC(50)-values of 2.2 μM (MMP-7) and 1.2 μM (MMP-13) that is selective over a broad range of MMP isoforms. It spares MMP-1, -2, -3, -8, -9, -12 and -14, making it a valuable modulator for targeted polypharmacology approaches.
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spelling pubmed-61515312018-11-13 Development of a Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-7/-13 Inhibitor Fischer, Thomas Riedl, Rainer Molecules Article Matrix metalloproteinase 7 (MMP-7) is a member of the MMP superfamily and is able to degrade extracellular matrix proteins such as casein, gelatin, fibronectin and proteoglycan. MMP-7 is a validated target for the development of small molecule drugs against cancer. MMP-13 is within the enzyme class the most efficient contributor to type II collagen degeneration and is a validated target in arthritis and cancer. We have developed the dual MMP-7/-13 inhibitor ZHAWOC6941 with IC(50)-values of 2.2 μM (MMP-7) and 1.2 μM (MMP-13) that is selective over a broad range of MMP isoforms. It spares MMP-1, -2, -3, -8, -9, -12 and -14, making it a valuable modulator for targeted polypharmacology approaches. MDPI 2017-09-14 /pmc/articles/PMC6151531/ /pubmed/32961647 http://dx.doi.org/10.3390/molecules22091548 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fischer, Thomas
Riedl, Rainer
Development of a Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-7/-13 Inhibitor
title Development of a Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-7/-13 Inhibitor
title_full Development of a Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-7/-13 Inhibitor
title_fullStr Development of a Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-7/-13 Inhibitor
title_full_unstemmed Development of a Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-7/-13 Inhibitor
title_short Development of a Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-7/-13 Inhibitor
title_sort development of a non-hydroxamate dual matrix metalloproteinase (mmp)-7/-13 inhibitor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151531/
https://www.ncbi.nlm.nih.gov/pubmed/32961647
http://dx.doi.org/10.3390/molecules22091548
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