TY - JOUR
T1 - Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases
AU - Chi, Victor
AU - Pennington, Michael William
AU - Norton, Raymond Stanley
AU - Tarcha, Eric J
AU - Londono, Luz M
AU - Sims-Fahey, Brian
AU - Upadhyay, Sanjeev K
AU - Lakey, Jonathan T
AU - Iadonato, Shawn
AU - Wulff, Heike
AU - Beeton, Christine
AU - Chandy, K George
PY - 2012
Y1 - 2012
N2 - Electrophysiological and pharmacological studies coupled with molecular identification have revealed a unique network of ion channels-Kv1.3, KCa3.1, CRAC (Orail + Stim1), TRPM7, Cl-swen-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. (C) 2011 Elsevier Ltd. All rights reserved.
AB - Electrophysiological and pharmacological studies coupled with molecular identification have revealed a unique network of ion channels-Kv1.3, KCa3.1, CRAC (Orail + Stim1), TRPM7, Cl-swen-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. (C) 2011 Elsevier Ltd. All rights reserved.
UR - http://www.journals.elsevier.com/toxicon/
U2 - 10.1016/j.toxicon.2011.07.016
DO - 10.1016/j.toxicon.2011.07.016
M3 - Article
VL - 59
SP - 529
EP - 546
JO - Toxicon
JF - Toxicon
SN - 0041-0101
IS - 4
ER -