Matrix metalloproteases (MMPs) are a family of zinc-dependent endopeptidases that collectively have the capacity to degrade virtually every component of the extracellular matrix (ECM). The characteristic domain structure of MMPs includes 4 domains. The catalytic domain, which is responsible for enzyme activity, contains the highly conserved Zn2+ binding region.
In most organs, the main components of the ECM are collagens and numerous other proteins that make up the basement membrane. Tumor cells overexpress proteases or induce the expression of these enzymes in neighboring stromal cells in order to degrade the basement membrane and invade the surrounding tissue. This proteolytic activity is also required for further metastasis. 
Due to the important roles that MMPs play in cancer, a number of matrix metalloproteinase inhibitors (MMPIs) have been investigated. Early inhibitors targeting MMP activity were designed to bind within the catalytic domain of these proteases. The initial therapeutics were peptidomimetics, or compounds derived from the sequences of the amino acids of the MMP’s endogenous ligands. Importantly, these compounds chelate the catalytic zinc ion in order to render the protease inactive. Small-molecules inhibitors such as CGS 27023A also target MMPs. An is propyl substituent α to the Zn2+-chelating hydroxamic acid moiety confers specificity by binding in the S10 subsite.  Another group of MMPIs is the chemically modified tetracyclines (CMTs). CMTs may inhibit MMPs by binding to the key metal ions or by regulating MMP transcription. 
 R. Roy, J. Yang, and M. A. Moses, “Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer,” J. Clin. Oncol., vol. 27, no. 31, pp. 5287–5297, 2009, doi: 10.1200/JCO.2009.23.5556.
 J. Cathcart, A. Pulkoski-Gross, and J. Cao, “Targeting matrix metalloproteinases in cancer: Bringing new life to old ideas,” Genes and Diseases, vol. 2, no. 1. Chongqing Medical University, pp. 26–34, Mar. 01, 2015, doi: 10.1016/j.gendis.2014.12.002.
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