Current Medicinal Chemistry

Author(s): Caterina Camodeca, Doretta Cuffaro, Elisa Nuti* and Armando Rossello

DOI: 10.2174/0929867325666180326164104

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ADAM Metalloproteinases as Potential Drug Targets

Page: [2661 - 2689] Pages: 29

  • * (Excluding Mailing and Handling)

Abstract

The ADAMs, together with ADAMTSs and snake venom metalloproteases (SVMPs), are members of the Adamalysin family. Differences in structural organization, functions and localization are known and their domains, catalytic or non-catalytic, show key roles in the substrate recognition and protease activity. Some ADAMs, as membrane-bound enzymes, show sheddase activity. Sheddases are key to modulation of functional proteins such as the tumor necrosis factor, growth factors, cytokines and their receptors, adhesion proteins, signaling molecules and stress molecules involved in immunity. These activities take part in the regulation of several physiological and pathological processes including inflammation, tumor growth, metastatic progression and infectious diseases. On these bases, some ADAMs are currently investigated as drug targets to develop new alternative therapies in many fields of medicine. This review will be focused on these aspects.

Keywords: Metalloendopeptidases, ectodomain shedding, adhesion molecules, hydroxamate inhibitors, zincbinding group, small molecules.