BRD4 inhibition for the treatment of pathological organ fibrosis

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Abstract

Fibrosis is defined as excess deposition of extracellular matrix, resulting in tissue scarring and organ dysfunction. It is estimated that 45% of deaths in the developed world are due to fibrosis-induced organ failure. Despite the well-accepted role of fibrosis in the pathogenesis of numerous diseases, there are only two US Food and Drug Administration–approved anti-fibrotic therapies, both of which are currently restricted to the treatment of pulmonary fibrosis. Thus, organ fibrosis represents a massive unmet medical need. Here, we review recent findings suggesting that an epigenetic regulatory protein, BRD4, is a nodal effector of organ fibrosis, and we highlight the potential of small-molecule BRD4 inhibitors for the treatment of diverse fibrotic diseases.

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Author and article information

Journal

Journal ID (nlm-ta): F1000Res

Journal ID (iso-abbrev): F1000Res

Journal ID (pmc): F1000Research

Title: F1000Research

Publisher: F1000Research (London, UK )

ISSN (Electronic): 2046-1402

Publication date (Electronic): 28 June 2017

Publication date Collection: 2017

Volume: 6

Electronic Location Identifier: F1000 Faculty Rev-1015

Affiliations

[1 ]Department of Medicine, Division of Cardiology and Consortium for Fibrosis Research & Translation, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA

[2 ]Gladstone Institutes and Department of Medicine, Division of Cardiology, University of California San Francisco School of Medicine, San Francisco, CA, USA

Author notes

[a ] timothy.mckinsey@ 123456ucdenver.edu

Competing interests: MSS and TAM declare that they have no competing interests. SMH is a scientific founder and shareholder of Tenava Therapeutics.

Author information

Timothy A. McKinsey http://orcid.org/0000-0001-7778-4470

Article

DOI: 10.12688/f1000research.11339.1

PMC ID: 5497817

PubMed ID: 28721198

SO-VID: 1b89546a-a14e-44ac-a95b-6c563f23fa56

License:

This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.