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BRD4 inhibition for the treatment of pathological organ fibrosis
Matthew S Stratton1, Saptarsi M Haldar2, Timothy A McKinsey1
1Department of Medicine, Division of Cardiology and Consortium for Fibrosis Research & Translation, University of Colorado, Anschutz Medical Campus, Aurora, CO, 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.
Insights
Fibrosis causes organ failure and death, with limited treatments. New research suggests targeting the BRD4 protein with inhibitors could treat various fibrotic diseases.
Area of Science:
- Epigenetics
- Molecular Biology
- Pathology
Background:
- Fibrosis, characterized by excess extracellular matrix deposition, leads to tissue scarring and organ dysfunction.
- Fibrosis contributes to 45% of deaths in developed nations, representing a significant unmet medical need.
- Current anti-fibrotic therapies approved by the FDA are limited to pulmonary fibrosis treatment.
Purpose of the Study:
- To review recent findings on the role of BRD4 in organ fibrosis.
- To highlight the therapeutic potential of small-molecule BRD4 inhibitors for diverse fibrotic diseases.
Main Methods:
- Literature review of recent studies on BRD4 and fibrosis.
- Analysis of the role of BRD4 as a nodal effector in fibrotic processes.
- Evaluation of small-molecule BRD4 inhibitors as a potential therapeutic strategy.
Main Results:
- Emerging evidence identifies BRD4 as a key regulator in the development of organ fibrosis.
- BRD4 inhibition presents a promising avenue for treating a wide range of fibrotic conditions.
Conclusions:
- BRD4 is a critical target for anti-fibrotic therapies.
- Small-molecule BRD4 inhibitors offer potential for treating diverse fibrotic diseases, addressing a major unmet medical need.
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