Discovery of novel potent migrastatic Thiazolo[5,4-b]pyridines targeting Lysyl-tRNA synthetase (KRS) for treatment of Cancer metastasis.
Animals
Antineoplastic Agents
/ chemical synthesis
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Dose-Response Relationship, Drug
Drug Discovery
Drug Screening Assays, Antitumor
Enzyme Inhibitors
/ chemical synthesis
Female
Humans
Lysine-tRNA Ligase
/ antagonists & inhibitors
Mammary Neoplasms, Experimental
/ diagnostic imaging
Mice
Mice, Inbred BALB C
Molecular Structure
Pyridines
/ chemical synthesis
Structure-Activity Relationship
Cell migration
Core scaffold hopping
Identification of binding pocket and residues
In vivo metastasis assay
Lysyl-tRNA synthetase
Migrastatics
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
05 Jun 2021
05 Jun 2021
Historique:
received:
19
11
2020
revised:
19
03
2021
accepted:
19
03
2021
pubmed:
9
4
2021
medline:
7
8
2021
entrez:
8
4
2021
Statut:
ppublish
Résumé
Recently, non-canonical roles of Lysyl-tRNA Synthetase (KRS), which is associated with cell migration and cancer metastasis, have been reported. Therefore, KRS has emerged as a promising target for the treatment of cell migration-related diseases, especially cancer metastasis, although the satisfying chemical inhibitors targeting KRS have not yet been identified. Here, we report the discovery of novel, mechanistically unique, and potent cell migration inhibitors targeting KRS, including the chemical and biological studies on the most effective N,N-dialkylthiazolo [5,4-b]pyridin-2-amine (SL-1910). SL-1910 exhibited highly potent migration inhibition (EC
Identifiants
pubmed: 33831781
pii: S0223-5234(21)00254-3
doi: 10.1016/j.ejmech.2021.113405
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Enzyme Inhibitors
0
Pyridines
0
Lysine-tRNA Ligase
EC 6.1.1.6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113405Informations de copyright
Copyright © 2021 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.