Carl Crysler;Lawrence C. Kuo;Kristi A. Leonard;Frank A. Lewandowski;Cynthi;Ingrid Christa Deckman;Carl Manthey;Richard Scott Alexander;Joseph Kent Barbay;Roger F. Bone;Paul F. Jackson;Diane M. Maguire
发明人:
Kristi A. Leonard,Richard Scott Alexander,Joseph Kent Barbay,Roger F. Bone,Carl Crysler,Ingrid Christa Deckman,Paul F. Jackson,Lawrence C. Kuo,Frank A. Lewandowski,Diane M. Maguire,Carl Manthey,Cynthi
申请号：
US13533131
公开号：
US08883473B2
申请日:
2012.06.26
申请国别(地区):
US
年份:
2014
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.
