CPP-beta18

CPP-beta18 is a novel 18-residue cell-penetrating peptide designed to selectively inhibit phosphatidylinositol 3-kinase beta (PI3Kβ). Developed by the Sheng lab at Virginia Tech Carilion School of Medicine, the peptide is derived from a specific motif in PI3Kβ that mediates its interaction with the regulatory protein p85. By blocking this interaction, CPP-beta18 selectively inhibits PI3Kβ activity with high affinity. It has demonstrated the ability to decrease cell viability and induce apoptosis in BRAF V600E/PTEN-null melanoma cell lines, which are particularly dependent on PI3Kβ signaling. The drug is being investigated as a potential combination therapy to enhance the efficacy of checkpoint inhibitors and overcome immunotherapy resistance in metastatic melanoma.