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

Toxicon. 2012 Mar 15;59(4):529-46. doi: 10.1016/j.toxicon.2011.07.016. Epub 2011 Aug 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 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*


  • Cnidarian Venoms
  • Immunologic Factors
  • Ion Channels
  • ShK neurotoxin