Janssen Pharmaceutica Nv

Yumanity Therapeutics, Inc.

Robert Scannevin

Kenneth Rhodes

Daniel Tardiff

Jeff Piotrowski

Rebecca Aron

Benjamin Vincent

Paul F Jackson

Eric Solis

Chee-Yeun Chung

Aihua Wang

Kristi A Leonard

Roger Francis Bone

Brett A Tounge

Barry A Springer

Joseph Kent Barbay

Bhaumik Pandya

Frank A Lewandowski

Cynthia M Milligan

Lawrence C Kuo

Matthew J Todd

Richard Scott Alexander

John Curtis Spurlino

Bertrand Le Bourdonnec

Matthew Lucas

Celine Schalk-Hihi

Diane M Maguire

Ingrid Christa Deckman

Matthew C Lucas

Parcharee Tivitmahaisoon

Iwona Wrona

Kerem Ozboya

Yue-Mei Zhang

Lawrence J Wilson

Shyh-Ming Yang

Carl L Manthey

Bangping Xiang

Xiaodong Fan

Prabha Saba Karnachi

Beverley Moore

Davraj Chakravarty

Carl Crysler

The present disclosure provides compounds and methods useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.

Methods for the treatment of neurological disorders

The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.

Compounds and uses thereof

The invention provides compositions and methods for treating neurological disorders, such as amyotrophic lateral sclerosis, frontotemporal degeneration, and Alzheimer's disease, among others. Using the compositions and methods described herein, a patient having a neurological disorder, such as a neurological disorder associated with TAR-DNA binding protein (TDP)-43 aggregation, may be administered an inhibitor of cytochrome P450 (CYP450) isoform 51A1 (CYP51A1), also referred to herein as lanosterol 14-alpha demethylase, so as to treat an underlying etiology of the disorder and/or to alleviate one or more symptoms of the disease. The inhibitor of CYP51A1 may be a small molecule, anti-CYP51A1 antibody or antigen-binding fragment thereof, or a compound, such as an interfering RNA molecule, that attenuates CYP51A1 expression. Patients that may be treated using the compositions and methods described herein include those that express a mutant TDP-43 isoform containing a mutation associated with TDP-43-promoted aggregation and toxicity.

Compositions and methods for the treatment and prevention of neurological disorders

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

This invention provides novel heterocyclic derived matrix metalloprotease inhibitors of the formula: and pharmaceutical compositions comprising same, useful for treating disorders ameliorated by antagonizing matrix metalloproteases. This invention also provides therapeutic and prophylactic methods using the instant pharmaceutical compositions.

Heterocyclic derived metalloprotease inhibitors

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Hopkinton, MA, United States of America

Robert Scannevin