1. Scaffold Repurposing of in-House Chemical Library toward the Identification of New Casein Kinase 1 δinhibitors
- Author
-
Gianpiero Spalluto, Alice Valentini, Maicol Bissaro, Mattia Sturlese, Stefano Moro, Maria Grazia Ferlin, Stephanie Federico, Eleonora Cescon, Giovanni Bolcato, Cescon, E., Bolcato, G., Federico, S., Bissaro, M., Valentini, A., Ferlin, M. G., Spalluto, G., Sturlese, M., and Moro, S.
- Subjects
chemistry.chemical_classification ,Scaffold ,Virtual screening ,consensus docking ,010405 organic chemistry ,In silico ,Organic Chemistry ,scaffold repurposing ,Computational biology ,Casein kinase 1 δ ,virtual screening ,01 natural sciences ,Biochemistry ,In vitro ,0104 chemical sciences ,Chemical library ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Enzyme ,chemistry ,Drug Discovery ,Casein kinase 1 ,Repurposing - Abstract
[Image: see text] 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.
- Published
- 2020