Scaffold Repurposing of in-House Chemical Library toward the Identification of New Casein Kinase 1 δ Inhibitors.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
11 Jun 2020
11 Jun 2020
Historique:
received:
19
01
2020
accepted:
28
04
2020
entrez:
20
6
2020
pubmed:
20
6
2020
medline:
20
6
2020
Statut:
epublish
Résumé
Recent studies have highlighted the key role of Casein kinase 1 δ (CK1δ) in the development of several neurodegenerative pathologies, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). So far, CK1δ inhibitors are noncovalent ATP competitive ligands and no drugs are currently available for this molecular target, hence the interest in developing new CK1δ inhibitors. The study aims to identify new inhibitors able to bind the enzyme; by a dual approach in silico/in vitro, the virtual screening has been performed on an in-house chemical library, which was previously designed and synthesized for other targets. The work can, therefore, be seen in the scaffold repurposing logic. The proposed strategy has led to the identification of two hits, having a novel scaffold in the landscape of CK1δ inhibitors and with an activity in the micromolar range.
Identifiants
pubmed: 32550997
doi: 10.1021/acsmedchemlett.0c00028
pmc: PMC7294733
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1168-1174Informations de copyright
Copyright © 2020 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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