title: Side-effects of protein kinase inhibitors on ion channels.
abstract: Protein kinases are one of the largest gene families and have regulatory roles in all aspects of eukaryotic cell function. Modulation of protein kinase activity is a desirable therapeutic approach for a number of human diseases associated with aberrant kinase activity, including cancers, arthritis and cardiovascular disorders. Several strategies have been used to develop specific and selective protein kinase modulators, primarily via inhibition of phosphorylation and down-regulation of kinase gene expression. These strategies are effective at regulating intracellular signalling pathways, but are unfortunately associated with several undesirable effects, particularly those that modulate ion channel function. In fact, the side-effects have precluded these inhibitors from being both useful experimental tools and therapeutically viable. This review focuses on the ion channel side-effects of several protein kinase inhibitors and specifically on those modulating K+, Na+ and Ca2+ ion channels. It is hoped that the information provided with a detailed summary in this review will assist the future development of novel specific and selective compounds targeting protein kinases both for experimental tools and for therapeutic approaches.
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Hongzoo
authors.initials: H
authors.lastname: Park
authors.forename: Amy L
authors.initials: AL
authors.lastname: Firth
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D049990:Membrane Transport Modulators / Q000009:adverse effects*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007473:Ion Channels; D049990:Membrane Transport Modulators; D047428:Protein Kinase Inhibitors