P9

P9 is an AI-designed therapeutic peptide optimized from the S372-382 sequence of the E6-associated protein (E6AP). It was developed using AI-assisted structural analysis to achieve high binding affinity for the high-risk human papillomavirus (hr-HPV) oncoprotein E6, specifically the HPV16 E6 variant. The primary mechanism of P9 involves disrupting the E6-E6AP protein-protein interaction, which is a critical step in the viral lifecycle that targets the tumor suppressor protein p53 for ubiquitination and subsequent proteasomal degradation. By blocking this interface, P9 restores p53 levels and its tumor-suppressive functions, leading to growth suppression in HPV16-driven cervical cancer cells. In experimental settings, P9 has also been conjugated with chemotherapy agents like camptothecin (forming Comp.1) to create dual-responsive compounds with improved intracellular delivery and synergistic anti-tumor activity.