| Literature DB >> 21867724 |
Victor Chi1, Michael W Pennington, Raymond S Norton, Eric J Tarcha, Luz M Londono, Brian Sims-Fahey, Sanjeev K Upadhyay, Jonathan T Lakey, Shawn Iadonato, Heike Wulff, Christine Beeton, K George Chandy.
Abstract
Electrophysiological and pharmacological studies coupled with molecular identification have revealed a unique network of ion channels--Kv1.3, KCa3.1, CRAC (Orai1 + Stim1), TRPM7, Cl(swell)--in lymphocytes that initiates and maintains the calcium signaling cascade required for activation. The expression pattern of these channels changes during lymphocyte activation and differentiation, allowing the functional network to adapt during an immune response. The Kv1.3 channel is of interest because it plays a critical role in subsets of T and B lymphocytes implicated in autoimmune disorders. The ShK toxin from the sea anemone Stichodactyla helianthus is a potent blocker of Kv1.3. ShK-186, a synthetic analog of ShK, is being developed as a therapeutic for autoimmune diseases, and is scheduled to begin first-in-man phase-1 trials in 2011. This review describes the journey that has led to the development of ShK-186. Copyright ÂEntities:
Mesh：
Substances：
Year: 2011 PMID： 21867724 PMCID： PMC3397671 DOI： 10.1016/j.toxicon.2011.07.016
Source DB: PubMed Journal: Toxicon ISSN： 0041-0101 Impact factor: 3.033