Patent Number: 8,798,939

Title: Methods for designing, selecting and/or optimizing allosteric processing inhibitors for matrix metalloproteinases

Abstract: 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.

Inventors: Leonard; Kristi A. (Lansdale, PA), Alexander; Richard Scott (Newark, DE), Barbay; Joseph Kent (Flourtown, PA), Bone; Roger F. (Bridgewater, NJ), Deckman; Ingrid Christa (Berwyn, PA), Jackson; Paul F. (Furlong, PA), Kuo; Lawrence C. (Gwynedd Valley, PA), Lewandowski; Frank A. (Philadelphia, PA), Maguire; Diane M. (Downingtown, PA), Milligan; Cynthia M. (Rutledge, PA), Rhodes; Kenneth J. (Belmont, MA), Scannevin; Robert H. (Hopkinton, MA), Schalk-Hihi; Celine (Phoenixville, PA), Springer; Barry (Wilmington, DE), Spurlino; John C. (Downingtown, PA), Todd; Matthew J. (Ambler, PA), Tounge; Brett A. (Blue Bell, PA), Wang; Aihua (Jamison, PA)

Assignee: Janssen Pharmaceutica N.V.

International Classification: G01N 33/48 (20060101); G01N 33/50 (20060101); G01N 31/00 (20060101)

Expiration Date: 8/05/12018