Janssen Pharmaceutica Nv

Carl Crysler

Aihua Wang

Kristi A Leonard

Roger Francis Bone

Brett A Tounge

Barry A Springer

Joseph Kent Barbay

Kenneth Rhodes

Lawrence C Kuo

Cynthia M Milligan

Frank A Lewandowski

Matthew J Todd

Richard Scott Alexander

Robert Scannevin

John Curtis Spurlino

Carl L Manthey

Celine Schalk-Hihi

Paul F Jackson

Diane M Maguire

Ingrid Christa Deckman

Beverley Moore

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.

Methods of treatment using allosteric processing inhibitors for matrix metalloproteinases

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Pottstown, PA, United States of America

Carl Crysler