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The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors

by 1,2,†, 2,3,†, 4,5 and 1,2,3,*
1
Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 4N1, Canada
2
McCaig Institute for Bone and Join Healthy, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada
3
Department of Physiology and Pharmacology, Cumming School of Medicine, Foothills Hospital, 3330 Hospital Dr, Calgary, AB T2N 4N1, Canada
4
Centre for Critical Illness Research, Victoria Research Labs, Lawson Health Research Institute, A6-134, London, ON N6A 5W9, Canada
5
Division of Respirology, Department of Medicine, Western University, London, ON N6A 5W9, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Pharmaceuticals 2021, 14(1), 31; https://doi.org/10.3390/ph14010031
Received: 5 December 2020 / Revised: 27 December 2020 / Accepted: 28 December 2020 / Published: 31 December 2020
(This article belongs to the Special Issue Novel Approaches for Targeting Metalloproteinases)
Matrix metalloproteinases (MMPs) have been demonstrated to have both detrimental and protective functions in inflammatory diseases. Several MMP inhibitors, with the exception of Periostat®, have failed in Phase III clinical trials. As an alternative strategy, recent efforts have been focussed on the development of more selective inhibitors or targeting other domains than their active sites through specific small molecule inhibitors or monoclonal antibodies. Here, we present some examples that aim to better understand the mechanisms of conformational changes/allosteric control of MMPs functions. In addition to MMP inhibitors, we discuss unbiased global approaches, such as proteomics and N-terminomics, to identify new MMP substrates. We present some examples of new MMP substrates and their implications in regulating biological functions. By characterizing the roles and substrates of individual MMP, MMP inhibitors could be utilized more effectively in the optimal disease context or in diseases never tested before where MMP activity is elevated and contributing to disease progression. View Full-Text
Keywords: matrix metalloproteinases (MMPs), protease; tissue inhibitors of metalloproteinases (TIMPs), exosite; small molecule inhibitors; monoclonal antibodies; proteomics; N-terminomics; terminal amine isotopic labeling of substrates (TAILS) matrix metalloproteinases (MMPs), protease; tissue inhibitors of metalloproteinases (TIMPs), exosite; small molecule inhibitors; monoclonal antibodies; proteomics; N-terminomics; terminal amine isotopic labeling of substrates (TAILS)
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MDPI and ACS Style

Das, N.; Benko, C.; Gill, S.E.; Dufour, A. The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors. Pharmaceuticals 2021, 14, 31. https://doi.org/10.3390/ph14010031

AMA Style

Das N, Benko C, Gill SE, Dufour A. The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors. Pharmaceuticals. 2021; 14(1):31. https://doi.org/10.3390/ph14010031

Chicago/Turabian Style

Das, Nabangshu, Colette Benko, Sean E. Gill, and Antoine Dufour. 2021. "The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors" Pharmaceuticals 14, no. 1: 31. https://doi.org/10.3390/ph14010031

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