Tat-SP4

Tat-SP4 is an autophagy-targeting stapled peptide designed for the treatment of small-cell lung cancer (SCLC). It consists of a stapled peptide sequence (SP4) conjugated to a Tat cell-penetrating peptide to enhance cellular uptake. Tat-SP4 enters cells primarily via macropinocytosis, a process that triggers extracellular calcium influx. Once inside, it induces a potent autophagic response that leads to autosis, a specific form of autophagy-dependent necrotic cell death. Additionally, the peptide causes mitochondrial dysfunction by impairing oxidative phosphorylation (OXPHOS) and reducing mitochondrial membrane potential. In preclinical studies, Tat-SP4 has demonstrated anti-proliferative effects in SCLC cell lines and inhibited tumor growth in xenograft models.