title: Identification of novel protein kinase CK1 delta (CK1delta) inhibitors through structure-based virtual screening.
abstract: 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 CK1delta inhibitors. These amino-anthraquinone analogs (derivatives 1 and 2) are among the most potent and selective CK1delta inhibitors known today (IC(50)=0.3 and 0.6 microM, respectively).
authors.affiliation: Molecular Modeling Section, Dipartimento di Scienze Farmaceutiche, Università di Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cozza
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gianoncelli
authors.forename: Monica
authors.initials: M
authors.lastname: Montopoli
authors.forename: Laura
authors.initials: L
authors.lastname: Caparrotta
authors.forename: Andrea
authors.initials: A
authors.lastname: Venerando
authors.forename: Flavio
authors.initials: F
authors.lastname: Meggio
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Pinna
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zagotto
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
mesh_terms: D000880:Anthraquinones / Q000737:chemistry; D047389:Casein Kinase I / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D010766:Phosphorylation; D020033:Protein Isoforms; D012984:Software; D014443:Tyrosine / Q000737:chemistry
chemical_list: D000880:Anthraquinones; D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D014443:Tyrosine; D047389:Casein Kinase I