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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Detalles Bibliográficos
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
Descripción
Sumario: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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