title: Potential clinical implications of recent matrix metalloproteinase inhibitor design strategies.
abstract: Analysis of matrix metalloproteinases (MMPs) expression profiles in various pathologies correlated with their presence in promoting disease progression. Drugs were designed to inhibit MMPs in an extreme manner by chelating the active site zinc ion. This approach did not distinguish between the 24 members of the MMP family and had devastating consequences during clinical trials. Subsequent knockout mouse studies showed that some MMPs are beneficial in regulating tumor growth, metastasis and indirectly stimulating the immune system. The broad-spectrum inhibitor approach was rethought and modified in order to increase specificity by taking into account the non-conserved secondary binding sites or differences in structures within MMPs and also generating antibodies. These showed interesting results in vitro and in vivo. The recent technological advances that allow us to better understand the function and structure of MMPs are aiding in the development of selective inhibitors.
authors.affiliation: a 1 Department of Chemistry & Biochemistry, Florida Atlantic University, 5353 Parkside Drive, Building MC17, Jupiter, FL 33458, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Amar
authors.affiliation: a 1 Department of Chemistry & Biochemistry, Florida Atlantic University, 5353 Parkside Drive, Building MC17, Jupiter, FL 33458, USA.|b 2 Department of Chemistry, The Scripps Research Institute/Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA.|c 3 Department of Chemistry and Biology, Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Fields
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors
keywords: antibody therapy; collagen; exosite; matrix metalloproteinase; selective inhibitor; triple-helical peptide