The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Discovery and Characterization of Small Molecule Inhibitors of the BET Family Bromodomains
Open accessAbstract
Epigenetic mechanisms of gene regulation have a profound role in normal development and disease processes. An integral part of this mechanism occurs through lysine acetylation of histone tails which are recognized by bromodomains. While the biological and structural characterization of many bromodomain containing proteins has advanced considerably, the therapeutic tractability of this protein family is only now becoming understood. This paper describes the discovery and molecular characterization of potent (nM) small molecule inhibitors that disrupt the function of the BET family of bromodomains (Brd2, Brd3, and Brd4). By using a combination of phenotypic screening, chemoproteomics, and biophysical studies, we have discovered that the protein-protein interactions between bromodomains and acetylated histones can be antagonized by selective small molecules that bind at the acetylated lysine recognition pocket. X-ray crystal structures of compounds bound into bromodomains of Brd2 and Brd4 elucidate the molecular interactions of binding and explain the precisely defined stereochemistry required for activity.
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Self-citationTargeting bromodomains: epigenetic readers of lysine acetylation
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Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4
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Target Identification for Small Bioactive Molecules: Finding the Needle in the Haystack
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Metadata
- Authors
- Chung, C.-W., Coste, H., White, J. H., Mirguet, O., Wilde, J., Gosmini, R. L., Delves, C., Magny, S. M., Woodward, R., Hughes, S. A., Boursier, E. V., Flynn, H., Bouillot, A. M., Bamborough, P., Brusq, J.-M. G., Gellibert, F. J., Jones, E. J., Riou, A. M., Homes, P., Martin, S. L., Uings, I. J., Toum, J., Clément, C. A., Boullay, A.-B., Grimley, R. L., Blandel, F. M., Prinjha, R. K., Lee, K., Kirilovsky, J., & Nicodeme, E.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-05-13
- Volume
- 54
- Issue
- 11
- Pages
- 3827-3838
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2155958514
- Cited by
- 334
- References
- 30
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Chung, C.-W., Coste, H., White, J. H., Mirguet, O., Wilde, J., Gosmini, R. L., Delves, C., Magny, S. M., Woodward, R., Hughes, S. A., Boursier, E. V., Flynn, H., Bouillot, A. M., Bamborough, P., Brusq, J.-M. G., Gellibert, F. J., Jones, E. J., Riou, A. M., Homes, P., . . . Nicodeme, E. (2011). Discovery and Characterization of Small Molecule Inhibitors of the BET Family Bromodomains. Journal of Medicinal Chemistry. https://doi.org/10.1021/jm200108t
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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