title: Casein kinases as potential therapeutic targets.
abstract: BACKGROUND
  The conventional term 'casein kinase' (CK) denotes three classes of kinases - CK1, CK2 and Golgi-CK (G-CK)/Fam20C (family with sequence similarity 20, member C) - sharing the ability to phoshorylate casein in vitro, but otherwise unrelated to each other. All CKs have been reported to be implicated in human diseases, and reviews individually dealing with the druggability of CK1 and CK2 are available. Our aim is to provide a comparative analysis of the three classes of CKs as therapeutic targets.
  
  
  METHODS
  CK2 is the CK for which implication in neoplasia is best documented, with the survival of cancer cells often relying on its overexpression. An ample variety of cell-permeable CK2 inhibitors have been developed, with a couple of these now in clinical trials. Isoform-specific CK1 inhibitors that are expected to play a beneficial role in oncology and neurodegeneration have been also developed. In contrast, the pathogenic potential of G-CK/Fam20C is caused by its loss of function. Activators of Fam20C, notably sphingolipids and their analogs, may prove beneficial in this respect.
  
  
  CONCLUSIONS
  Optimization of CK2 and CK1 inhibitors will prove useful to develop new therapeutic strategies for treating cancer and neurodegenerative disorders, while the design of potent activators of G-CK/Fam20C will provide a new tool in the fields of bio-mineralization and hypophosphatemic diseases.
authors.affiliation: a 1 University of Padova, Department of Biomedical Sciences , Via Ugo Bassi 58B, 35131 Padova, Italy giorgio.cozza@unipd.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cozza
authors.affiliation: a 1 University of Padova, Department of Biomedical Sciences , Via Ugo Bassi 58B, 35131 Padova, Italy giorgio.cozza@unipd.it.|b 2 University of Padova, Department of Biomedical Sciences and CNR Institute of Neurosciences , Padova, Italy ; lorenzo.pinna@unipd.it.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Pinna
mesh_terms: D000818:Animals; D047389:Casein Kinase I / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017674:Hypophosphatemia / Q000188:drug therapy; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D016326:Extracellular Matrix Proteins; D047428:Protein Kinase Inhibitors; D047389:Casein Kinase I; D047390:Casein Kinase II; C524449:FAM20C protein, human
keywords: Fam20C; cancer; casein kinase 1; casein kinase 2; casein kinases; hypophosphatemia; kinase activators; kinase inhibitors; neurodegenerative diseases; phosphorylation