Peptides have emerged as a therapeutically and commercially important drug class with the advantage of excellent specificity and potency as well as low toxicity. In addition, peptides are invaluable research tools to investigate the physiological functions of receptors and the underlying mechanisms of diseases. Peptide research has innovated the understanding and treatment of numerous diseases, including diabetes, cancer, pain, obesity, HIV, multiple sclerosis, and gastrointestinal disorders, with currently >80 peptide therapeutics approved and >150 peptides in clinical trials.
Despite the promise of venom-derived drug discovery, only a few venom-derived drugs have made it into the market, raising the question of where the bottlenecks in (pre)clinical development are and what can be done to improve this. We try to analyse this and provide an overview of the latest developments, trends and opportunities in venom-based drug discovery. We also provide examples from our lab, including how we study and overcome the intrinsic susceptibility to proteolytic degradation and lack of oral bioavailability, molecular approaches to improve target engagement, and new directions and opportunities for venom-based drug discovery and development in the areas of pain and gastrointestinal disorders.