Janssen Pharmaceutica Nv

Yumanity Therapeutics, Inc.

Massachusetts Institute of Technology

Whitehead Institute for Biomedical Research

Daniel Tardiff

Kenneth Rhodes

Robert Scannevin

Rebecca Aron

Jeff Piotrowski

Bhaumik Pandya

Benjamin Vincent

Eric Solis

Chee-Yeun Chung

Matthew C Lucas

Bertrand Le Bourdonnec

Parcharee Tivitmahaisoon

Iwona Wrona

Matthew Lucas

Kerem Ozboya

Stephen L Buchwald

Susan Lindquist

Nathan Jui

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 provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and pharmaceutical compositions thereof. The present invention also provides methods and kits using the inventive compounds and pharmaceutical compositions for treating and/or preventing diseases associated with protein aggregation, such as amyloidoses (e.g., Parkinson's disease and Alzheimer's disease), treating and/or preventing neurodegenerative diseases, treating and/or preventing diseases associated with Tar DNA binding protein 43 kDa, reducing or preventing protein aggregation, and/or modulating E3 ubiquitin ligase in a subject in need thereof. 

Benzimidazole derivatives and uses thereof

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Arlington, MA, United States of America

Daniel Tardiff