Peptide inhibitors targeting Ras and Ras-associated protein-protein interactions

Peptides represent attractive molecules for targeting protein-protein interactions, and peptide drug development has made great progress during the last decades. Ras protein, the most promising target in cancer therapy, is one of the major growth drivers in various cancers. Although many small molecule inhibitors have been reported to effectively target Ras protein and some inhibitors (such as MRTX849 and AMG 510) have been translated into clinical application, just a few peptide inhibitors have been reported. Here we summarize different types of peptide inhibitors, including monocyclic peptides, bicyclic peptides, stapled peptides, and proteomimetic inhibitors, developed in recent years; emphasize the limits and achievements; and discuss the outlook and challenges associated with future research in peptide inhibitors. This review aims to provide a reference for the discovery of Ras peptide inhibitors.