Janssen Pharmaceutica Nv

Janssen Research & Development, LLC

Matthew J Todd

Sui-Po Zhang

Stephen M Prouty

Marina I Nelen

Erica L Nulton

Aihua Wang

Kristi A Leonard

Roger Francis Bone

Chris Flores

Brett A Tounge

Joseph Kent Barbay

Barry A Springer

Kenneth Rhodes

Cynthia M Milligan

Frank A Lewandowski

Lawrence C Kuo

Robert Scannevin

Richard Scott Alexander

John Curtis Spurlino

Paul F Jackson

Diane M Maguire

Celine Schalk-Hihi

Ingrid Christa Deckman

Mark J Macielag

Bin Benjamin Zhu

Mark E McDonnell

Scott L Dax

Li Liu

Jose Clemente

Kristen Chevalier

Christopher M Flores

Carl L Manthey

Matthew Olson

James K Kranz

Gabrielle C Todd

Carl Crysler

Beverley Moore

Mark E Mcdonnell

Barry Springer

Robert H Scannevin

Kenneth J Rhodes

Kristen M Chevalier

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

Disclosed are compounds, compositions and methods for treating diseases, syndromes, conditions and disorders that are affected by the inhibition of MGL, including pain. Such compounds are represented by Formula (I) as follows: 

Heteroaromatic and aromatic piperazinyl azetidinyl amides as monoacylglycerol lipase inhibitors

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

Disclosed are compounds, compositions and methods for treating diseases, syndromes, conditions and disorders that are affected by the inhibition of MGL, including pain. Such compounds are represented by Formula (I) as follows:  are defined herein.

A method for identifying a ligand or compound which binds to albumin comprises the steps of contacting a reaction mixture comprising a site-specific probe and albumin in the presence and the absence of the ligand or compound and measuring either dissociation constant K, inhibitor concentration ICor fluorescence displacement; whereby a change in K, ICand/or fluorescence in the presence of the ligand or compound is indicative of the ligand or compound binds to albumin.

Assay for evaluating affinity and specificity of ligand-albumin binding

A method of screening a compound which modulates dipeptidyl peptidase I (DPPI) activities comprises the steps of adding a peptide substrate of DPPI to a reaction mixture which comprises DPPI and a compound, wherein the peptide substrate of DPPI has at least 3 amino acids and binds to a binding site of DPPI in addition to the S-Ssite; and measuring the molecular weight of the substrate, wherein a change in the molecular weight of the substrate is indicative of the presence of DPPI activity.

High-throughput assay for evaluating dipeptidyl peptidase I activity

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Ambler, PA, United States of America

Matthew J Todd