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High resolution crystal structure of BRD4-BD1 in complex with a novel inhibitor precursor.
Ma, Xiuxiu; Wang, Meng; Wang, Fan; Li, Jiao; Zhang, Zhengguang; Zhu, Jiapeng; Liu, Bing.
Afiliação
  • Ma X; School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
  • Wang M; School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
  • Wang F; School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
  • Li J; School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
  • Zhang Z; School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
  • Zhu J; School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 2100
  • Liu B; School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China. Electronic address: bingliu@njucm.edu.cn.
Biochem Biophys Res Commun ; 690: 149284, 2024 Jan 01.
Article em En | MEDLINE | ID: mdl-38006801
The inhibition of BRD4 bromodomain is an effective therapeutic strategy for a variety of diseases in which BRD4 are implicated. Herein, we identified a small-molecule BRD4 inhibitor hit named compound 3 using high-throughput screening. The 1.6 Å resolution co-crystal structure confirmed that the compound occupies the KAc recognition pockets of BRD4 by forming key hydrogen bonds with Asn140 and engaging in hydrophobic interactions, thus impedes the binding of acetylated lysine to BRD4. These findings suggest compound 3 can be a lead compound to develop a structurally novel BRD4 inhibitors.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Proteínas de Ciclo Celular Idioma: En Revista: Biochem Biophys Res Commun Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Proteínas de Ciclo Celular Idioma: En Revista: Biochem Biophys Res Commun Ano de publicação: 2024 Tipo de documento: Article