Prediction of an MMP-1 inhibitor activity cliff using the SAR matrix approach and its experimental validation

A matrix metalloproteinase 1 (MMP-1) inhibitor activity cliff was predicted using the SAR Matrix method. Compound 4 was predicted as a highly potent activity cliff partner and found to possess 60 times higher inhibitory activity against MMP-1 than the structurally related compound 3. Furthermore, ph...

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Autores principales: Asawa, Yasunobu, Yoshimori, Atsushi, Bajorath, Jürgen, Nakamura, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477548/
https://www.ncbi.nlm.nih.gov/pubmed/32895466
http://dx.doi.org/10.1038/s41598-020-71696-2
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author Asawa, Yasunobu
Yoshimori, Atsushi
Bajorath, Jürgen
Nakamura, Hiroyuki
author_facet Asawa, Yasunobu
Yoshimori, Atsushi
Bajorath, Jürgen
Nakamura, Hiroyuki
author_sort Asawa, Yasunobu
collection PubMed
description A matrix metalloproteinase 1 (MMP-1) inhibitor activity cliff was predicted using the SAR Matrix method. Compound 4 was predicted as a highly potent activity cliff partner and found to possess 60 times higher inhibitory activity against MMP-1 than the structurally related compound 3. Furthermore, pharmacophore fitting of synthesized compounds indicated that the correctly predicted activity cliff was caused by interactions between the trifluoromethyl group at para position in compound 4 and residue ARG214 of MMP-1.
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spelling pubmed-74775482020-09-08 Prediction of an MMP-1 inhibitor activity cliff using the SAR matrix approach and its experimental validation Asawa, Yasunobu Yoshimori, Atsushi Bajorath, Jürgen Nakamura, Hiroyuki Sci Rep Article A matrix metalloproteinase 1 (MMP-1) inhibitor activity cliff was predicted using the SAR Matrix method. Compound 4 was predicted as a highly potent activity cliff partner and found to possess 60 times higher inhibitory activity against MMP-1 than the structurally related compound 3. Furthermore, pharmacophore fitting of synthesized compounds indicated that the correctly predicted activity cliff was caused by interactions between the trifluoromethyl group at para position in compound 4 and residue ARG214 of MMP-1. Nature Publishing Group UK 2020-09-07 /pmc/articles/PMC7477548/ /pubmed/32895466 http://dx.doi.org/10.1038/s41598-020-71696-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Asawa, Yasunobu
Yoshimori, Atsushi
Bajorath, Jürgen
Nakamura, Hiroyuki
Prediction of an MMP-1 inhibitor activity cliff using the SAR matrix approach and its experimental validation
title Prediction of an MMP-1 inhibitor activity cliff using the SAR matrix approach and its experimental validation
title_full Prediction of an MMP-1 inhibitor activity cliff using the SAR matrix approach and its experimental validation
title_fullStr Prediction of an MMP-1 inhibitor activity cliff using the SAR matrix approach and its experimental validation
title_full_unstemmed Prediction of an MMP-1 inhibitor activity cliff using the SAR matrix approach and its experimental validation
title_short Prediction of an MMP-1 inhibitor activity cliff using the SAR matrix approach and its experimental validation
title_sort prediction of an mmp-1 inhibitor activity cliff using the sar matrix approach and its experimental validation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477548/
https://www.ncbi.nlm.nih.gov/pubmed/32895466
http://dx.doi.org/10.1038/s41598-020-71696-2
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