Bromodomain and Extra-Terminal Family Protein Inhibitors: A Potentially New Therapy for Heart Disease

Abstract

Bromodomain-containing protein 4 (BRD4) is a member of the mammalian bromoand extra-terminal domain (BET) protein family, which also comprises BRD2, BRD3, and testis-specific BRDt. The BET family of proteins shares the structure of two evolutionarily conserved tandem N-terminal bromodomains, as well as an extra-terminal (ET) domain (Figure 1). They bind acetylated histone tails through bromodomains, which results in localization to the chromosome, where they recruit other regulatory complexes, such as transcription elongation factor b (P-TEFb) and mediators, to influence gene expression [1,2]. In 2010, two groups independently discovered JQ1 and I-BET as BET bromodomain inhibitors, a class of small molecules that forms monovalent interactions with individual BET bromodomains that compete for binding of bromodomains to their natural ligand, acetylated Abstract