The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that promotes the expression of phase I and II xenobiotic chemical metabolizing enzyme genes, including the cytochrome P450 (CYP) isoforms CYP1A1 and CYP1A2. Phortress is a lysyl amide prodrug of the benzothiazole 5-fluoro 203 , a high affinity AhR ligand that elicits antitumor activity by inducing transcription of CYP1A1, which leads to the formation of DNA adducts and cell cycle arrest. Phortress rapidly reverts to 5-fluoro 203 in carcinoma cell lines, resulting in significant growth inhibition at nanomolar concentrations. At 20 mg/kg, phortress can suppress the growth of breast and ovarian xenografts in vivo.
