Abstract
Agonists of the aryl hydrocarbon receptor (AhR), which in turn induce their own metabolism by cytochrome P-450 isozymes (e.g., CYP1A1) to produce cytotoxic species selectively within cancer cells, represent attractive anticancer drug development candidates. The concept of utilizing the AhR pathway as a vehicle to induce selective cytotoxicity in cancer cells, however, remains untested in the clinic to date. The most promising agents in this class are the 2-(4-aminophenyl)benzothiazole prodrug Phortress (University of Nottingham/Nationai Cancer institute [NCI] Developmental Therapeutics) and a fluorinated diaminoflavone (Kyowa Hakko/NCI Developmental Therapeutics); both agents are currently in advanced preclinicai development. The development of selective antitumor agents targeting the AhR pathway will be reviewed here, and an assessment made of their clinical potential.
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