Sp-sc7

Sp-sc7 (also known as sP-sc7) is a cell-permeable, α-helical stapled peptide designed to restore the p53 tumor suppressor pathway in cancer cells. Developed by Aileron Therapeutics and researchers at Harvard University, Sp-sc7 acts as a potent dual antagonist of MDM2 and MDMX (MDM4), the two primary negative regulators of p53. By mimicking the alpha-helical transactivation domain of p53, the peptide competitively binds to the p53-binding pockets of MDM2 and MDMX, thereby preventing p53 ubiquitination and degradation. The 'stapling' technique—utilizing a hydrocarbon cross-link—stabilizes the peptide's secondary structure, which enhances its binding affinity, protects it from proteolytic degradation, and facilitates cellular uptake. Sp-sc7 served as a critical lead compound in the development of clinical-stage stapled peptides like ALRN-6924 for the treatment of wild-type p53-expressing malignancies.

Other names

stapled p53 peptide sc7