Bromodomain biology and drug discovery

• Published in: Nature structural & molecular biology Vol. 26; no. 10; pp. 870 - 879
• Main Authors: Zaware, Nilesh, Zhou, Ming-Ming
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2019; Nature Publishing Group
• Subjects: 631/154; 631/337/100/2285; 631/337/176; 631/337/458/1275; Acetylation - drug effects; Animals; Biochemistry; Biological Microscopy; Biology; Biomedical and Life Sciences; Cancer; Care and treatment; Chromatin; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA repair; Drug Discovery - methods; Epigenesis, Genetic - drug effects; Epigenetic inheritance; Gene expression; Genetic aspects; Health aspects; Histone Code - drug effects; Histones - chemistry; Histones - genetics; Humans; Inflammation; Inflammation - drug therapy; Inflammation - genetics; Inflammatory diseases; Life Sciences; Lysine; Membrane Biology; Models, Molecular; Neoplasms - drug therapy; Neoplasms - genetics; Pathogenesis; Protein Domains - drug effects; Protein interaction; Protein Structure; Protein-protein interactions; Proteins; Recombination; Review Article; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Structure; Transcription; Transcription Factors - chemistry; Transcription Factors - genetics; United States
• ISSN: 1545-9993; 1545-9985; 1545-9985
• DOI: 10.1038/s41594-019-0309-8

The bromodomain (BrD) is a conserved structural module found in chromatin- and transcription-associated proteins that acts as the primary reader for acetylated lysine residues. This basic activity endows BrD proteins with versatile functions in the regulation of protein-protein interactions mediating chromatin-templated gene transcription, DNA recombination, replication and repair. Consequently, BrD proteins are involved in the pathogenesis of numerous human diseases. In this Review, we highlight our current understanding of BrD biology, and discuss the latest development of small-molecule inhibitors targeting BrDs as emerging epigenetic therapies for cancer and inflammatory disorders. Zaware and Zhou review the current understanding of bromodomain biology and discuss the latest development of small-molecule inhibitors that target these protein domains as emerging therapies for cancer and inflammatory disorders.