CPP-β18

CPP-β18 is a novel 18-residue cell-penetrating peptide (CPP) designed to selectively inhibit the beta isoform of phosphatidylinositol 3-kinase (PI3Kβ). Developed by the Sheng lab at the Virginia Tech Carilion School of Medicine, the peptide is derived from a specific structural motif unique to PI3Kβ that facilitates its interaction with the p85 regulatory subunit. By mimicking this motif, CPP-β18 competitively disrupts the PI3Kβ-p85 interface, thereby preventing kinase activation and downstream signaling. Preclinical studies in BRAF V600E/PTEN-null melanoma models have demonstrated that CPP-β18 significantly reduces cell viability and induces apoptosis in cells that hyper-express PI3Kβ. The agent is currently being investigated as a potential sensitizing therapy to enhance the efficacy of immune checkpoint inhibitors and overcome innate or acquired resistance in metastatic melanoma.