The "elusive DMOAD": Aggrecanase inhibition from laboratory to clinic.

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  • Author(s): Malfait AM;Malfait AM; Tortorella MD; Tortorella MD
  • Source:
    Clinical and experimental rheumatology [Clin Exp Rheumatol] 2019 Sep-Oct; Vol. 37 Suppl 120 (5), pp. 130-134. Date of Electronic Publication: 2019 Oct 15.
  • Publication Type:
    Journal Article; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Clinical And Experimental Rheumatology S.A.S Country of Publication: Italy NLM ID: 8308521 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0392-856X (Print) Linking ISSN: 0392856X NLM ISO Abbreviation: Clin Exp Rheumatol Subsets: MEDLINE
    • Publication Information:
      Publication: Pisa : Clinical And Experimental Rheumatology S.A.S
      Original Publication: Pisa, Italy : Pacini editore, [1983-
    • Subject Terms:
      ADAM Proteins*/antagonists & inhibitors ; ADAM Proteins*/immunology ; Procollagen N-Endopeptidase*; Endopeptidases/*metabolism ; Osteoarthritis/*enzymology; ADAMTS4 Protein ; Aggrecans/metabolism ; Humans ; Osteoarthritis/drug therapy ; Osteoarthritis/immunology
    • Abstract:
      From the time of their discovery in 1999, the aggrecanases, and ADAMTS-5 in particular, have been heavily investigated as targets for disease-modifying osteoarthritis drug (DMOAD) development. Here, we provide a brief narrative review of the discovery efforts to target these enzymes, and how this led to the current ongoing programmes that hold promise for the future. We discuss a comparison of inhibition of collagen breakdown versus inhibition of aggrecan breakdown. We then summarise existing programmes that target ADAMTS-5, including small molecule inhibitors, monoclonal neutralising antibodies and nanobodies, and gene editing technologies. We also briefly discuss the potential analgesic effects this strategy may offer in addition to its joint-protective effects.
    • Accession Number:
      0 (Aggrecans)
      EC 3.4.- (Endopeptidases)
      EC 3.4.24.- (ADAM Proteins)
      EC 3.4.24.14 (Procollagen N-Endopeptidase)
      EC 3.4.24.82 (ADAMTS4 Protein)
      EC 3.4.99.- (aggrecanase)
    • Publication Date:
      Date Created: 20191018 Date Completed: 20191028 Latest Revision: 20191028
    • Publication Date:
      20250114
    • Accession Number:
      31621572