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Scaffold Repurposing of in-House Chemical Library toward the Identification of New Casein Kinase 1 δinhibitors

Cescon E.
•
Cescon E.
•
Bolcato G.
altro
Moro S.
2020
  • journal article

Periodico
ACS MEDICINAL CHEMISTRY LETTERS
Abstract
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, CK1δinhibitors are noncovalent ATP competitive ligands and no drugs are currently available for this molecular target, hence the interest in developing new CK1δinhibitors. 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 CK1δinhibitors and with an activity in the micromolar range.
DOI
10.1021/acsmedchemlett.0c00028
WOS
WOS:000541747800018
Archivio
http://hdl.handle.net/11368/2969048
info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85087087230
https://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.0c00028
Diritti
closed access
license:copyright editore
FVG url
https://arts.units.it/request-item?handle=11368/2969048
Soggetti
  • Casein kinase 1 δ

  • consensus docking

  • scaffold repurposing

  • virtual screening

Web of Science© citazioni
7
Data di acquisizione
Mar 20, 2024
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