- 专利标题： Crystal Structure of the Pro Form of a Matrix Metalloproteinase and an Allosteric Processing Inhibitor
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申请号： US13533108申请日： 2012-06-26
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公开(公告)号： US20130040360A1公开(公告)日： 2013-02-14
- 发明人: Kristi A. Leonard , Richard Scott Alexander , Joseph Kent Barbay , Roger F. Bone , Ingrid Christa Deckman , Paul F. Jackson , Lawrence C. Kuo , Frank A. Lewandowski , Diane M. Maguire , Cynthia M. Milligan , Kenneth J. Rhodes , Robert H. Scannevin , Celine Schalk-Hihi , Barry Springer , John C. Spurlino , Matthew J. Todd , Brett Andrew Tongue , Aihua Wang
- 申请人： Kristi A. Leonard , Richard Scott Alexander , Joseph Kent Barbay , Roger F. Bone , Ingrid Christa Deckman , Paul F. Jackson , Lawrence C. Kuo , Frank A. Lewandowski , Diane M. Maguire , Cynthia M. Milligan , Kenneth J. Rhodes , Robert H. Scannevin , Celine Schalk-Hihi , Barry Springer , John C. Spurlino , Matthew J. Todd , Brett Andrew Tongue , Aihua Wang
- 主分类号： C12N9/96
- IPC分类号： C12N9/96
摘要：
The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues. The present invention also relates to the use of small-molecule allosteric processing inhibitors for the treatment of diseases mediated by inappropriate matrix metalloproteinase (MMP) activity.