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Discovery and lead identification of quinazoline-based BRD4 inhibitors.
Yang, Shyh-Ming; Urban, Daniel J; Yoshioka, Makoto; Strovel, Jeffrey W; Fletcher, Steven; Wang, Amy Q; Xu, Xin; Shah, Pranav; Hu, Xin; Hall, Matthew D; Jadhav, Ajit; Maloney, David J.
Afiliação
  • Yang SM; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States. Electronic address: yangs9@mail.nih.gov.
  • Urban DJ; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
  • Yoshioka M; ConverGene LLC., 3093 Beverly Lane, Unit C, Cambridge, MD 21613, United States.
  • Strovel JW; ConverGene LLC., 3093 Beverly Lane, Unit C, Cambridge, MD 21613, United States.
  • Fletcher S; Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, MD 21201, United States.
  • Wang AQ; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
  • Xu X; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
  • Shah P; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
  • Hu X; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
  • Hall MD; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
  • Jadhav A; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
  • Maloney DJ; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States. Electronic address: dave@NexusDA.com.
Bioorg Med Chem Lett ; 28(21): 3483-3488, 2018 11 15.
Article em En | MEDLINE | ID: mdl-30268702
ABSTRACT
A new series of quinazoline-based analogs as potent bromodomain-containing protein 4 (BRD4) inhibitors is described. The structure-activity relationships on 2- and 4-position of quinazoline ring, and the substitution at 6-position that mimic the acetylated lysine are discussed. A co-crystallized structure of 48 (CN750) with BRD4 (BD1) including key inhibitor-protein interactions is also highlighted. Together with preliminary rodent pharmacokinetic results, a new lead (65, CN427) is identified which is suitable for further lead optimization.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinazolinas / Fatores de Transcrição / Proteínas Nucleares Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinazolinas / Fatores de Transcrição / Proteínas Nucleares Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article