Selective inhibition of BET bromodomains.

Journal article

Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal ...

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Authors: Filippakopoulos, P; Qi, J; Picaud, S; Shen, Y; Smith, W

• Publication status: Published
• Journal: Nature
• Volume: 468
• Issue: 7327
• Pages: 1067-1073
• Publication date: 2010-12-01
• DOI: 10.1038/nature09504
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: Protein Binding; Female; Humans; Models, Molecular; Dihydropyridines; Nuclear Proteins; Protein Structure, Tertiary; Skin Neoplasms; Carcinoma, Squamous Cell; Transcription Factors; Recombinant Proteins; Sequence Alignment; Mice; Molecular Sequence Data; Cell Proliferation; Cell Differentiation; Binding Sites; Cell Line, Tumor; Azirines; Chromatin; Stereoisomerism; Amino Acid Sequence; Animals; Mice, Nude