α-amanitin

**α-Amanitin** is a highly toxic bicyclic octapeptide toxin primarily found in *Amanita phalloides* (death cap mushroom) and other species like *Galerina marginata*. It potently and irreversibly inhibits **eukaryotic RNA polymerase II** by binding to its bridging helix, preventing RNA translocation and transcription elongation, which blocks mRNA synthesis and leads to rapid hepatocyte cytolysis. With an oral LD50 of ~0.1 mg/kg in humans, it causes delayed but fatal liver failure; emerging applications include use as a payload in **antibody-drug conjugates (ADCs)** for therapy-resistant cancers due to its activity in non-dividing, multidrug-resistant cells at picomolar concentrations and low aggregation tendency.[1][2][3]

Other names

alpha-amanitinamanitin