Design, synthesis, and antitumor activity of stapled peptide inhibitors targeting the RAS-RAF interactions.

RAS-RAF interactions play a vital role in the RAS-RAF-MEK-ERK signaling pathway, significantly regulating cell proliferation, differentiation, and survival. Some small molecule inhibitors targeting various components of this pathway, such as MRTX849 and AMG 510, have been introduced for clinical application. However, peptide-based drugs encounter several challenges, such as poor cell permeability, low biological stability, and rapid in vivo clearance, which hinder their application.