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Progress and challenges in the optimization of toxin peptides for development as pain therapeutics.

The number of new toxin peptide discoveries has been rapidly growing in the past few decades. Because of progress in proteomics, sequencing technologies, and high throughput bioassays, the search for new toxin peptides from venom collections and potency optimization has become manageable. However, to date, only six toxin peptide-derived therapeutics have been approved by the USFDA, with only one, ziconotide, for a pain indication. The challenge of venom-derived peptide therapeutic development remains in improving selectivity to the target and more importantly, in delivery of these peptides to the sites of action in the central and peripheral nervous system. In this review, we highlight peptide toxins that target major therapeutic targets for pain and discuss the challenges of developing toxin peptides as potential therapeutics.

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