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

BRD4 inhibition for the treatment of pathological organ fibrosis

Matthew S Stratton  1 , Saptarsi M Haldar  2 , Timothy A McKinsey  1
Affiliations
Review

BRD4 inhibition for the treatment of pathological organ fibrosis

Matthew S Stratton et al. F1000Res. .

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.

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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.

Figures

Figure 1.
Figure 1.. A model for the regulation of pathological organ fibrosis by BRD4.
Stress signals, such as those elicited by transforming growth factor-beta (TGF-β), trigger recruitment of BRD4 to regulatory regions (super-enhancers, typical enhancers, and promoters) of genes that drive organ fibrosis. Bromodomain and extra-terminal (BET) inhibitors prevent association of BRD4 with these loci and thus suppress pro-fibrotic gene expression.
See this image and copyright information in PMC

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