Novel SAR for quinazoline inhibitors of EHMT1 and EHMT2.
Binding Sites
Cell Line, Tumor
Drug Design
Enzyme Inhibitors
/ chemistry
Histocompatibility Antigens
/ genetics
Histone-Lysine N-Methyltransferase
/ antagonists & inhibitors
Histones
/ metabolism
Humans
Inhibitory Concentration 50
Lysine
/ chemistry
Molecular Docking Simulation
Pancreatic Neoplasms
/ metabolism
Point Mutation
Quinazolines
/ chemistry
Structure-Activity Relationship
EHMT1
EHMT2
Epigenetics
Histone Lysine Methyl Transferase (HMKT)
Quinazoline
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
01 09 2019
01 09 2019
Historique:
received:
23
12
2018
revised:
28
05
2019
accepted:
11
06
2019
pubmed:
28
7
2019
medline:
17
9
2020
entrez:
28
7
2019
Statut:
ppublish
Résumé
Detailed structure activity relationship of two series of quinazoline EHMT1/EHMT2 inhibitors (UNC0224 and UNC0638) have been elaborated. New and active alternatives are presented for the ubiquitous substitution patterns found in literature for the linker to the lysine mimicking region and the lysine mimic itself. These findings could allow for advancing EHMT1/EHMT2 inhibitors of that type beyond tool compounds by fine-tuning physicochemical properties making these inhibitors more drug-like. .
Identifiants
pubmed: 31350126
pii: S0960-894X(19)30392-0
doi: 10.1016/j.bmcl.2019.06.012
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Histocompatibility Antigens
0
Histones
0
Quinazolines
0
EHMT1 protein, human
EC 2.1.1.-
EHMT2 protein, human
EC 2.1.1.43
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2516-2524Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.