Improved Stapled Peptide Suppresses Tumor Growth In Rodents

Peptides play many important roles in the human body. They don’t always translate smoothly, however, into drugs that control human physiology. One promising strategy to convert peptides into therapies is “stapling”—reinforcing floppy helical motifs with a hydrocarbon brace. A biotech company that specializes in stapled peptides now reports an improved lead for cancer therapies (Proc. Natl. Acad. Sci. USA 2013, DOI: 10.1073/pnas.1303002110). The peptide, ATSP-7041(shown), stifles tumor growth in rodents by restoring the activity of vital tumor suppressor p53. Tomi K. Sawyer and his team at Aileron Therapeutics took inspiration from SAH-p53-8, a stapled peptide designed to prevent a protein called MDM2 from masking p53. That stapled peptide had limited activity in the company’s most stringent tests. To make improvements, Aileron teamed with Lyubomir T. Vassilev and colleagues at Roche, a firm that has brought to human clinical trials molecules targeting the p53-MDM2 interaction. In tests on cells, the fruit of their collaboration, ATSP-7041, had a prolonged effect on p53 compared with RG7112, a Roche drug candidate in early-stage clinical trials.