Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases.
Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases.
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DOI：
10.1016/j.toxicon.2011.07.016
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发表时间：
2012-03-15
期刊：
影响因子：
2.8
通讯作者：
Chandy, K. George
中科院分区：
文献类型：
--
作者：
Chi, Victor;Pennington, Michael W.;Norton, Raymond S.;Tarcha, Eric J.;Londono, Luz M.;Sims-Fahey, Brian;Upadhyay, Sanjeev K.;Lakey, Jonathan T.;Iadonato, Shawn;Wulff, Heike;Beeton, Christine;Chandy, K. George
关键词：
电生理和药理学研究结合分子鉴定揭示了淋巴细胞中一个独特的离子通道网络-Kv1.3、KCa3.1、CRAC(Orai1+STIM1)、TRPM7、Clswell-启动和维持激活所需的钙信号级联。这些通道的表达模式在淋巴细胞激活和分化过程中发生变化，允许功能网络在免疫反应期间进行适应。Kv1.3通道之所以令人感兴趣，是因为它在T和B淋巴细胞亚群中发挥着关键作用，这些T和B淋巴细胞亚群与自身免疫性疾病有关。来自海葵Stichodactyla heliantus的ShK毒素是Kv1.3的有效阻断剂。ShK-186是ShK的合成类似物，正在开发中，用于治疗自身免疫性疾病，并计划于2011年开始第一人阶段试验。这篇综述描述了导致ShK-186发展的历程。
Electrophysiological and pharmacological studies coupled with molecular identification have revealed a unique network of ion channels—Kv1.3, KCa3.1, CRAC (Orai1 + Stim1), TRPM7, Clswell—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.
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影响因子：
64.8
作者：
DECOURSEY, TE;CHANDY, KG;CAHALAN, MD
通讯作者：
CAHALAN, MD
影响因子：
3.7
作者：
Fasth, AER;Cao, D;Malmström, V
通讯作者：
Malmström, V
DOI：
10.1073/pnas.0402455101
发表时间：
2004-07-27
影响因子：
11.1
作者：
Corcione, A;Casazza, S;Pistoia, V
通讯作者：
Pistoia, V
影响因子：
6.5
作者：
Azam, Philippe;Sankaranarayanan, Ananthakrishnan;Wulff, Heike
通讯作者：
Wulff, Heike
影响因子：
2.6
作者：
Dörner, T;Lipsky, P
通讯作者：
Lipsky, P