4-O-Demethylpenclomedine

DMPEN (4,o-demethylpenclomedine) is the highly reactive principal alkylating metabolite of Penclomedine (PEN), a multichlorinated alpha-picoline derivative. DM-PEN’s proposed mechanism of action begins with activation by free radical formation in the liver, where it is then transported to tumor cells via the circulation system. The free radical moiety forms an adduct with DNA, and interstrand crosslinking occurs through the 5-chloro moiety. The 5-chloro moiety is then activated by keto-enol tautomerism, producing the alkylating group, an alpha-haloketo function.