Discovery of DB18, a potent inhibitor of CLK kinases with a high selectivity against DYRK1A kinase.
Antineoplastic Agents
/ chemical synthesis
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
Drug Discovery
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Protein Kinase Inhibitors
/ chemical synthesis
Protein Serine-Threonine Kinases
/ antagonists & inhibitors
Protein-Tyrosine Kinases
/ antagonists & inhibitors
Structure-Activity Relationship
Dyrk Kinases
Cancer
Kinases
Molecular modelling
Quinazolines
Triazoles
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
received:
19
10
2020
revised:
11
12
2020
accepted:
16
12
2020
pubmed:
11
1
2021
medline:
1
9
2021
entrez:
10
1
2021
Statut:
ppublish
Résumé
We describe in this paper the synthesis of a novel series of anilino-2-quinazoline derivatives. These compounds have been screened against a panel of eight mammalian kinases and in parallel they were tested for cytotoxicity on a representative panel of seven cancer cell lines. One of them (DB18) has been found to be a very potent inhibitor of human "CDC2-like kinases" CLK1, CLK2 and CLK4, with IC
Identifiants
pubmed: 33422908
pii: S0968-0896(20)30792-6
doi: 10.1016/j.bmc.2020.115962
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Protein Kinase Inhibitors
0
Protein-Tyrosine Kinases
EC 2.7.10.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115962Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.