Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Pharmacological Tails of Matrix Metalloproteinases and Their Inhibitors

Version 1 : Received: 5 December 2020 / Approved: 7 December 2020 / Online: 7 December 2020 (15:07:30 CET)

A peer-reviewed article of this Preprint also exists.

Das, N.; Benko, C.; Gill, S.E.; Dufour, A. The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors. Pharmaceuticals 2021, 14, 31. Das, N.; Benko, C.; Gill, S.E.; Dufour, A. The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors. Pharmaceuticals 2021, 14, 31.

Journal reference: Pharmaceuticals 2020, 14, 31
DOI: 10.3390/ph14010031

Abstract

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 (e.g., exosites, ectosites) 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 and achieve a better understanding of the roles of these proteases in diseases.

Subject Areas

Matrix metalloproteinase; MMPs; protease; TIMPs; exosite; small molecule inhibitors; monoclonal antibodies; proteomics; N-terminomics; TAILS

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