Structure–Activity Relationship Study of <i>N</i><sup>6</sup>-Benzoyladenine-Type BRD4 Inhibitors and Their Effects on Cell Differentiation and TNF-α Production
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- Amemiya Seika
- Institute of Molecular & Cellular Biosciences, The University of Tokyo
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- Yamaguchi Takao
- Institute of Molecular & Cellular Biosciences, The University of Tokyo
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- Sakai Taki
- Institute of Molecular & Cellular Biosciences, The University of Tokyo
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- Hashimoto Yuichi
- Institute of Molecular & Cellular Biosciences, The University of Tokyo
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- Noguchi-Yachide Tomomi
- Institute of Molecular & Cellular Biosciences, The University of Tokyo
Bibliographic Information
- Other Title
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- Structure-Activity Relationship Study of N⁶-Benzoyladenine-Type BRD4 Inhibitors and Their Effects on Cell Differentiation and TNF-α Production
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Abstract
<p>Bromodomains are epigenetic ‘readers’ of histone acetylation. The first potent bromodomain and extra-terminal domain (BET) inhibitors, (+)-JQ1 and I-BET762 (also known as GSK525762), were reported in 2010. Some BET inhibitors are already under clinical trial for the treatment of cancers, but so far, only a few chemical scaffolds are available. We have reported potent N6-benzoyladenine-based inhibitors of BRD4, a BET family member that serves as a key mediator of transcriptional elongation. Here we present an analysis of the structure–activity relationships of these inhibitors. Among the compounds examined, 20, 28 and 29 enhanced all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation and inhibited tumor necrosis factor (TNF)-α production by THP-1 cells.</p>
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 64 (9), 1378-1383, 2016
The Pharmaceutical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390001204176516992
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- NII Article ID
- 130005261607
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- NII Book ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 027565552
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- PubMed
- 27581642
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed