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F1000Res. 2017 Jun 28;6. pii: F1000 Faculty Rev-1015. doi: 10.12688/f1000research.11339.1. eCollection 2017.

BRD4 inhibition for the treatment of pathological organ fibrosis.

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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.

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.

KEYWORDS:

BRD4; anti-fibrotic therapies; fibrotic diseases; organ fibrosis; small molecule BRD4 inhibitors

Conflict of interest statement

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

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