Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases

被引：175

作者：

Chi, Victor ^{[1
]}

Pennington, Michael W. ^{[3
]}

Norton, Raymond S. ^{[4
]}

Tarcha, Eric J.

Londono, Luz M. ^{[5
]}

Sims-Fahey, Brian ^{[5
]}

Upadhyay, Sanjeev K. ^{[1
]}

Lakey, Jonathan T. ^{[2
]}

Iadonato, Shawn

Wulff, Heike ^{[6
]}

Beeton, Christine ^{[7
]}

Chandy, K. George ^{[1
]}

机构：

[1] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Dept Surg, Irvine, CA 92697 USA

[3] Peptides Int, Louisville, KY 40299 USA

[4] Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia

[5] Kineta Inc, Seattle, WA 98199 USA

[6] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA

[7] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA

来源：

TOXICON | 2012年 / 59卷 / 04期

基金：

英国医学研究理事会;

关键词：

Autoimmune; ShK; BgK; Sea anemone; Toxin; T cell; B cell; Kv1.3; KCa3.1; Potassium channel; CRAC; Multiple sclerosis; Rheumatoid arthritis; Type-1; diabetes mellitus; ShK-186; PAP-1; Psoriasis; Transplant; ShK-192; GATED POTASSIUM CHANNEL; MEMORY T-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CD27(HIGH) PLASMA-CELLS; MOLECULE KV1.3 BLOCKER; CENTRAL-NERVOUS-SYSTEM; SHK TOXIN; MULTIPLE-SCLEROSIS; K+ CHANNELS; IMMUNOLOGICAL SYNAPSE;

D O I：

10.1016/j.toxicon.2011.07.016

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：529 / 546

页数：18

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