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**4S5NG-PE24** is a fusion protein designed for targeted melanoma therapy. It combines the cell-penetrating peptide 4S5NG, which selectively binds to **integrin α6** on melanoma cells, with the cytotoxic toxin **PE24**, a truncated variant of Pseudomonas exotoxin A. 4S5NG-PE24 induces cell death specifically in integrin α6-expressing melanoma through **caspase-3/gasdermin E-dependent pyroptosis**, and triggers a systemic antitumor immune response. The drug shows potent, selective cytotoxicity in vitro and in vivo, and, when combined with PD-1 checkpoint blockade, can maximize antitumor efficacy. Preclinical safety studies demonstrate no significant off-target toxicity or organ damage at therapeutic doses[1].
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