VP-1-16 undergoes O-demethylation to generate active intermediates that binds to protein and DNA. The O-demethylation is P450 dependent. Peroxidases, such as horseradish or prostaglandin synthetase, also activate VP-16 and VM-26 to their O-Quinonderivatives, and catalyze binding of reactive intermediates to DNA. Enzymatic activation to reactive intermediates may be important in the biological activities of VP-16 and VM-26.