Article ; Online: Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases.
Toxicon : official journal of the International Society on Toxinology
2011 Volume 59, Issue 4, Page(s) 529–546
Abstract: ... 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 ...
| 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. |
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| MeSH term(s) | Amino Acid Sequence ; Animals ; Autoimmune Diseases/drug therapy ; Cell Differentiation/drug effects ; Cnidarian Venoms/pharmacokinetics ; Cnidarian Venoms/pharmacology ; Drug-Related Side Effects and Adverse Reactions ; Immunologic Factors/pharmacokinetics ; Immunologic Factors/pharmacology ; Ion Channels/metabolism ; Lymphocyte Activation/drug effects ; Molecular Sequence Data ; Protein Conformation ; Sea Anemones |
| Chemical Substances | Cnidarian Venoms ; Immunologic Factors ; Ion Channels ; ShK neurotoxin |
| Language | English |
| Publishing date | 2011-08-12 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review |
| ZDB-ID | 204479-1 |
| ISSN | 1879-3150 ; 0041-0101 |
| ISSN (online) | 1879-3150 |
| ISSN | 0041-0101 |
| DOI | 10.1016/j.toxicon.2011.07.016 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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