Molecular design of new aggrecanases-2 inhibitors.

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  • Author(s): Shan ZJ;Shan ZJ; Zhai HL; Huang XY; Li LN; Zhang XY
  • Source:
    Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Oct 01; Vol. 23 (19), pp. 5339-50. Date of Electronic Publication: 2013 Aug 02.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9107377 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3405 (Electronic) Linking ISSN: 0960894X NLM ISO Abbreviation: Bioorg Med Chem Lett Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Elsevier Science Ltd
      Original Publication: Oxford ; New York : Pergamon Press, c1991-
    • Subject Terms:
      Computer Simulation* ; Drug Design*; ADAM Proteins/*antagonists & inhibitors ; Enzyme Inhibitors/*chemistry; ADAMTS5 Protein ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Humans ; Models, Molecular ; Protein Binding/drug effects ; Quantitative Structure-Activity Relationship
    • Abstract:
      Aggrecanases-2 is a very important potential drug target for the treatment of osteoarthritis. In this study, a series of known aggrecanases-2 inhibitors was analyzed by the technologies of three-dimensional quantitative structure-activity relationships (3D-QSAR) and molecular docking. Two 3D-QSAR models, which based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods, were established. Molecular docking was employed to explore the details of the interaction between inhibitors and aggrecanases-2 protein. According to the analyses for these models, several new potential inhibitors with higher activity predicted were designed, and were supported by the simulation of molecular docking. This work propose the fast and effective approach to design and prediction for new potential inhibitors, and the study of the interaction mechanism provide a better understanding for the inhibitors binding into the target protein, which will be useful for the structure-based drug design and modifications.
      (Copyright © 2013 Elsevier Ltd. All rights reserved.)
    • Contributed Indexing:
      Keywords: Aggrecanase-2; Inhibitor; Molecular design; Molecular docking; Quantitative structure–activity relationship
    • Accession Number:
      0 (Enzyme Inhibitors)
      EC 3.4.24.- (ADAM Proteins)
      EC 3.4.24.- (ADAMTS5 Protein)
      EC 3.4.24.- (ADAMTS5 protein, human)
    • Publication Date:
      Date Created: 20130820 Date Completed: 20140407 Latest Revision: 20161125
    • Publication Date:
      20250114
    • Accession Number:
      10.1016/j.bmcl.2013.07.060
    • Accession Number:
      23953188