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Discovery and Optimization of Selective Inhibitors of Meprin α (Part II)
Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997411/ https://www.ncbi.nlm.nih.gov/pubmed/33673639 http://dx.doi.org/10.3390/ph14030197 |
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author | Wang, Chao Diez, Juan Park, Hajeung Becker-Pauly, Christoph Fields, Gregg B. Spicer, Timothy P. Scampavia, Louis D. Minond, Dmitriy Bannister, Thomas D. |
author_facet | Wang, Chao Diez, Juan Park, Hajeung Becker-Pauly, Christoph Fields, Gregg B. Spicer, Timothy P. Scampavia, Louis D. Minond, Dmitriy Bannister, Thomas D. |
author_sort | Wang, Chao |
collection | PubMed |
description | Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). Here, in part II, we report further efforts to optimize potency and selectivity. We hope that a hydroxamic acid meprin α inhibitor probe will help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition. |
format | Online Article Text |
id | pubmed-7997411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79974112021-03-27 Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) Wang, Chao Diez, Juan Park, Hajeung Becker-Pauly, Christoph Fields, Gregg B. Spicer, Timothy P. Scampavia, Louis D. Minond, Dmitriy Bannister, Thomas D. Pharmaceuticals (Basel) Article Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). Here, in part II, we report further efforts to optimize potency and selectivity. We hope that a hydroxamic acid meprin α inhibitor probe will help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition. MDPI 2021-02-27 /pmc/articles/PMC7997411/ /pubmed/33673639 http://dx.doi.org/10.3390/ph14030197 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Wang, Chao Diez, Juan Park, Hajeung Becker-Pauly, Christoph Fields, Gregg B. Spicer, Timothy P. Scampavia, Louis D. Minond, Dmitriy Bannister, Thomas D. Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
title | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
title_full | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
title_fullStr | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
title_full_unstemmed | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
title_short | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
title_sort | discovery and optimization of selective inhibitors of meprin α (part ii) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997411/ https://www.ncbi.nlm.nih.gov/pubmed/33673639 http://dx.doi.org/10.3390/ph14030197 |
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