LEONARD, KRISTI A.,ALEXANDER, RICHARD SCOTT,BONE, ROGER F.,CRYSLER, CARL,DECKMAN, INGRID CHRISTA,JACKSON, PAUL F.,KUO, LAWRENCE C.,LEWANDOWSKI, FRANK A.,MAGUIRE, DIANE M.,MANTHEY, CARL,MILLIGAN, CYNTH
申请号：
CA2840393
公开号：
CA2840393A1
申请日:
2012.06.26
申请国别(地区):
CA
年份:
2013
代理人:
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.
