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Cardiovascular disease

BET inhibitor attenuates heart failure

Nature Reviews Drug Discovery volume 16, page 453 (2017)Cite this article

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Patients with systolic HF are typically given antagonists of β-adrenergic receptors and of the renin–angiotensin axis, which decrease the levels of stress-induced hormones and also reduce left ventricular (LV) remodelling. However, the 5-year mortality after an initial diagnosis of HF is 40%, so new treatments are needed. Previous work from this group showed that BRD4 is a critical co-activator of pathologic gene transactivation during cardiomyocyte hypertrophy, and that the BRD4 inhibitor JQ1 could prevent the development of cardiac hypertrophy and LV dysfunction if administered at the onset of pressure overload in mice.

Compared with placebo, JQ1 reduced signs of HF

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References

  1. Duan, Q. et al. BET bromodomain inhibition suppresses innate inflammatory and profibrotic transcriptional networks in heart failure. Sci. Transl Med. 9, eaah5084 (2017)

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  1. Megan Cully
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Filippakopoulos, P. & Knapp, S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov. 13, 337–356 (2014)

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Cully, M. BET inhibitor attenuates heart failure. Nat Rev Drug Discov 16, 453 (2017). https://doi.org/10.1038/nrd.2017.125

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