Identification of novel protein kinase CK1 delta (CK1δ) inhibitors through structure-based virtual screening

In eukaryotes, protein phosphorylation of serine, threonine or tyrosine residues by protein kinases plays an important role in many cellular processes. Members of the protein kinase CK1 family usually phosphorylate residues of serine that are close to other phosphoserine in a consensus motif of pS-X-X-S, and they are implicated in the regulation of a variety of physiological processes as well as in pathologies like cancer and Alzheimer’s disease. Using a structure-based virtual screening (SBVS) approach we have identified two anthraquinones as novel CK1δ inhibitors. These amino-anthraquinone analogs (derivatives 1 and 2) are among the most potent and selective CK1δ inhibitors known today (IC50 = 0.3 and 0.6 μM, respectively).

Graphical abstractUsing a structure-based virtual screening (SBVS) approach we have identified two anthraquinones as novel CK1δ inhibitors. These compounds are among the most potent and selective CK1δ inhibitors known today (IC50 = 0.3 and 0.6 μM, respectively).Figure optionsDownload full-size imageDownload as PowerPoint slide