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

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.