Melittin (MEL)

Melittin is a cytolytic amphipathic peptide made up of 26 amino acids and constitutes the principal active toxin and pain-inducing component in honeybee (Apis mellifera) venom, accounting for 40–60% of venom dry weight[1][2][3]. It binds to lipid bilayers, assumes an α-helical structure, and disrupts cell membranes, producing rapid lysis of a wide range of cell types[1][2][3]. As such, it plays an essential defensive role for bees, causing pain and tissue damage in predators. In research settings, melittin has been widely studied as both a model membrane-active peptide and a prototype cytolytic toxin. Investigational therapeutic interest has centered on its antimicrobial, antiviral, and especially anticancer effects; melittin can suppress activation of EGFR and HER2 in some cancer cell types and induce apoptotic cell death in vitro and in vivo[4][5]. However, its clinical utility is severely limited by non-specific toxicity, hemolysis, and the risk of severe allergic reactions[1][5]. Melittin is not a canonical drug target in humans (it is a direct acting toxin, not a receptor or enzyme), but an exogenous, bioactive peptide with potential uses as a template for therapeutic development or as a cytolytic agent in targeted delivery strategies[1][2][5][6].

Disrupts cell membranes by forming pores, leading to cell lysis\nInduces apoptosis and necrosis via membrane permeability and downstream signaling\nInhibits phosphorylation/activity of EGFR and HER2 receptors (in cancer research)\nBlocks Na⁺/K⁺-ATPase and other membrane transporters