Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins
| Autor: | Carine Derviaux, Stefan Knapp, Yuliia V. Voitovich, Brigitt Raux, Stéphane Priet, Jean Michel Brunel, Yves Collette, Sabine Milhas, Stephane Betzi, Eric Trinquet, Alexey Yu. Fedorov, Philippe Roche, Thomas Roux, Etienne Rebuffet, Adrien Lugari, Sebastien Combes, Jean-Claude Guillemot, Xavier Morelli |
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| Přispěvatelé: | Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine BRD4 Cell Cycle Proteins 01 natural sciences 03 medical and health sciences Protein structure Transcription (biology) Drug Discovery Humans Cell Cycle Protein ComputingMilieux_MISCELLANEOUS [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] 010405 organic chemistry Chemistry Drug discovery Nuclear Proteins Acetylation [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] In vitro Protein Structure Tertiary 3. Good health 0104 chemical sciences Bromodomain [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] 030104 developmental biology Biochemistry Xanthines Molecular Medicine Transcription Factors |
| Zdroj: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, American Chemical Society, 2016, 59 (4, SI), pp.1634-1641. ⟨10.1021/acs.jmedchem.5b01708⟩ Journal of Medicinal Chemistry, 2016, 59 (4, SI), pp.1634-1641. ⟨10.1021/acs.jmedchem.5b01708⟩ |
| ISSN: | 0022-2623 1520-4804 |
| DOI: | 10.1021/acs.jmedchem.5b01708⟩ |
| Popis: | A midthroughput screening follow-up program targeting the first bromodomain of the human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with an affinity in the low micromolar range yet exerts suitable unexpected selectivity in vitro against the other members of the bromodomain and extra-terminal domain (BET) family. A structure-based program pinpointed a role of the ZA loop, paving the way for the development of potent and selective BET-BRDi probes. |
| Databáze: | OpenAIRE |
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