CYP4F Enzymes are the Major Enzymes in Human Liver Microsomes that Catalyze the O-Demethylation of the Antiparasitic Prodrug DB289

DB289 is a prodrug that is converted by several steps to the active metabolite DB75. DB289 exhibits enhanced oral efficacy and reduced acute toxicity over DB75, an aromatic dicationic compound that is effective against a broad range of pathogens in vitro including African trypanosomiasis (African sleeping sickness). This reaction phenotyping study aimed to identify the enzymes responsible for oxidative O-demethylation; the first step in this conversion to DB75.