Humantenine is a highly toxic indole alkaloid derived from Gelsemium elegans. It specifically targets RNA m6A modification regulatory proteins, including ALKBH5 and METTL, where it binds stably through hydrogen bonding and hydrophobic interactions. This binding disrupts m6A methylation levels of target genes, leading to impaired expression of intestinal epithelial cell tight junction and cytoskeleton-related genes, ultimately resulting in intestinal barrier dysfunction and substantial cytotoxicity. In animal studies, Humantenine exhibits an intraperitoneal LD50 of less than 1 mg/kg in mice. Its metabolism varies across species, with notable demethylation, dehydrogenation, and oxidation observed in liver microsomes of humans, pigs, goats, and rats.
Humantenine is a highly toxic indole alkaloid derived from Gelsemium elegans. It specifically targets RNA m6A modification regulatory proteins, including ALKBH5 and METTL, where it binds stably through hydrogen bonding and hydrophobic interactions. This binding disrupts m6A methylation levels of target genes, leading to impaired expression of intestinal epithelial cell tight junction and cytoskeleton-related genes, ultimately resulting in intestinal barrier dysfunction and substantial cytotoxicity. In animal studies, Humantenine exhibits an intraperitoneal LD50 of less than 1 mg/kg in mice. Its metabolism varies across species, with notable demethylation, dehydrogenation, and oxidation observed in liver microsomes of humans, pigs, goats, and rats.
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