Resumen de Chapter Twenty-One - Advancements in Stapled Peptide Drug Discovery & Development
Vincent Guerlavais, Tomi K. Sawyer
Abstract Stapled peptides are an emerging class of drugs with a unique set of properties that fully capitalize on 25 years of genetic research to attack drivers of complex diseases, including cancer, endocrine/metabolic disorders, and inflammation. Stapling technology locks peptides into their biologically active shape and impart unprecedented pharmaceutical stability within the body. Stapled peptide drugs are derived from natural peptides and are designed to potently and specifically target protein–protein interactions both inside and outside the cell. The review highlights the first example of a potent and selective stapled peptide dual inhibitor of MDM2 and MDMX, ATSP-7041 that reactivates p53-dependent pathway in multiple cancer cell lines in vitro and in vivo. This new class of drugs represents a fundamentally new therapeutic approach to modulate signaling pathways to treat human disease.
