Conus Venoms - A Rich Source of Peptide-Based Therapeutics
Tiffany S. Han, Russell W. Teichert, Baldomero M. Olivera and Grzegorz Bulaj
Pages 2462-2479 (18)
Over two decades of research on venom peptides derived from cone snails (“conopeptides or conotoxins”) has led to several compounds that have reached human clinical trials, most of them for the treatment of pain. Remarkably, none of the conopeptides in clinical development mediate analgesia through the opioid receptors, underlying the diverse and novel neuropharmacology evolved by Conus snails. These predatory animals produce an estimated ∼100,000 distinct conotoxins, a vast majority yet to be discovered and characterized. The conopeptides studied to-date in animal models, have exhibited antinociceptive, antiepileptic, neuroprotective or cardioprotective activities. Screening results also suggest applications of conotoxins in cancer, neuromuscular and psychiatric disorders. Additional potentially important applications of conotoxin research are the discovery and validation of new therapeutic targets, also defining novel binding sites on already validated molecular targets. As the structural and functional diversity of conotoxins is being investigated, the Conus venoms continue to surprise with the plethora of neuropharmacological compounds and potential new therapeutics. This review summarizes recent efforts in the discovery of conopeptides, and their preclinical and clinical development.
Conotoxins, Conus peptides, conopeptides, drug discovery, preclinical development
Department of Medicinal Chemistry, College of Pharmacy, University of Utah, 421 Wakara Way,Suite 360, Salt Lake City, Utah 84108, USA.