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Cardiovascular disease

Heart failure

BET bromodomain

Cell culture and rodent studies suggest BET bromodomain inhibitors could help treat heart failure. In rodent and human heart tissue, the BET bromodomain-containing protein bromodomain containing 4 (BRD4) was strongly expressed. In neonatal rat ventricular cardiomyocytes, a series of BET bromodomain inhibitors decreased hypertrophy compared with vehicle control. In the transverse aortic constriction mouse model of cardiac hypertrophy, a BET bromodomain inhibitor improved cardiac function and decreased histological features of heart failure compared with vehicle. Next steps could include testing BET bromodomain inhibition in additional animal models.
Tensha Therapeutics Inc., cofounded by James Bradner, has the BET bromodomain inhibitor TEN-010 in preclinical development for cancer.
At least three other companies have BET bromodomain inhibitors in Phase I testing or preclinical development to treat cancer.

SciBX 6(34); doi:10.1038/scibx.2013.928
Published online Sept. 5, 2013

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Anand, P. et al. Cell;
published online Aug. 1, 2013;
Contact: Saptarsi M. Haldar,
Case Western Reserve University School of Medicine, Cleveland, Ohio
Contact: James E. Bradner,
Dana-Farber Cancer Institute, Boston, Mass.