Conotoxin therapeutics: a pipeline for success?

The pharmacopoeia of conotoxins from the marine snail Conus has evolved with time, providing a myriad of molecular scaffolds on which critical, molecular pharmacophoric descriptors, responsible for mediating conotoxin receptor-target specificity and selectivity have been grafted. Several reports have defined how these critical determinants contribute to refined, subtype-selective receptor recognition. However, the clinical utility of conotoxins is debatable with a single conotoxin, ω-MVIIA (ziconotide), approved by the US FDA. The authors review the present status of conotoxin-based drug discovery efforts, highlighting ongoing preclinical and clinical studies, while discussing strategies that may be necessary to overcome the barriers inherent to peptide therapeutics. Through the beauty of nature and the art of design it should be possible to expand the Conus pipeline.