Janssen Pharmaceutica Nv

Ortho-mcneil Pharmaceutical Corp.

3-dimensional Pharmaceuticals, Inc.

Ingrid Christa Deckman

John Curtis Spurlino

Aihua Wang

Kristi A Leonard

Roger Francis Bone

Brett A Tounge

Joseph Kent Barbay

Barry A Springer

Kenneth Rhodes

Frank A Lewandowski

Cynthia M Milligan

Lawrence C Kuo

Robert Scannevin

Richard Scott Alexander

Matthew J Todd

Diane M Maguire

Celine Schalk-Hihi

Paul F Jackson

Carl L Manthey

Carsten Schubert

Bruce L Grasberger

Anthony Sapienza

Beverley Moore

Diane Maguire

Dale S Dhanoa

Declan E Ryan

Carl Crysler

Barry Springer

Robert H Scannevin

Kenneth J Rhodes

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

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

Crystal structure of the pro form of a matrix metalloproteinase and an allosteric processing inhibitor

The present invention includes crystallized HDM2 peptides as well as descriptions of the X-ray diffraction patterns of the crystals. The diffraction patterns allow the three dimensional structure of HDM2 to be determined at atomic resolution so that ligand binding sites on HDM2 can be identified and the interactions of ligands with HDM2 amino acid residues can be modeled. Models prepared using such maps permit the design of ligands which can function as active agents which include, but are not limited to, those that function as inhibitors of MDM2 and HDM2 oncoproteins.

HDM2-inhibitor complexes and uses thereof

Substituted thiazoles and the use thereof as inhibitors of plasminogen activator inhibitor-1

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Berwyn, PA, United States of America

Ingrid Christa Deckman