BRD4 inhibition for the treatment of pathological organ fibrosis

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

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.

Publication types

  • Review

Grants and funding

TAM was supported by the National Institutes of Health (NIH) (HL116848 and HL127240) and the American Heart Association (16SFRN31400013). SMH was funded by the NIH (HL127240 and DK093821). MSS was supported by a T32 training grant and an F32 fellowship from the NIH (5T32HL007822 and F32HL126354).