Methods of treatment using allosteric processing inhibitors for matrix metalloproteinases

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 th...

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Bibliographische Detailangaben
Hauptverfasser:	JACKSON PAUL F, SCANNEVIN ROBERT H, ALEXANDER RICHARD SCOTT, KUO LAWRENCE C, CRYSLER CARL, LEONARD KRISTI A, BONE ROGER F, SPURLINO JOHN C, LEWANDOWSKI FRANK A, TODD MATTHEW J, DECKMAN INGRID CHRISTA, SCHALK-HIHI CELINE, TOUNGE BRETT A, MOORE BEVERLEY, MAGUIRE DIANE M, MANTHEY CARL, BARBAY JOSEPH KENT, RHODES KENNETH J, MILLIGAN CYNTHIA M, WANG AIHUA, SPRINGER BARRY
Format:	Patent
Sprache:	eng
Schlagworte:	HUMAN NECESSITIES HYGIENE MEDICAL OR VETERINARY SCIENCE PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS
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Beschreibung
Zusammenfassung:	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.