Application of Atypical Acetyl-lysine Methyl Mimetics in the Development of Selective Inhibitors of the Bromodomain-Containing Protein 7 (BRD7)/Bromodomain-Containing Protein 9 (BRD9) Bromodomains.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
11 06 2020
11 06 2020
Historique:
pubmed:
16
5
2020
medline:
13
11
2020
entrez:
16
5
2020
Statut:
ppublish
Résumé
Non-BET bromodomain-containing proteins have become attractive targets for the development of novel therapeutics targeting epigenetic pathways. To help facilitate the target validation of this class of proteins, structurally diverse small-molecule ligands and methodologies to produce selective inhibitors in a predictable fashion are in high demand. Herein, we report the development and application of atypical acetyl-lysine (KAc) methyl mimetics to take advantage of the differential stability of conserved water molecules in the bromodomain binding site. Discovery of the
Identifiants
pubmed: 32410449
doi: 10.1021/acs.jmedchem.0c00075
doi:
Substances chimiques
BRD7 protein, human
0
BRD9 protein, human
0
Chromosomal Proteins, Non-Histone
0
Ligands
0
Pyridazines
0
Transcription Factors
0
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM