Cytochrome P450s (CYPs) are heme-containing enzymes, that catalyze a number of phase I metabolism reactions. Human CYP1A1 is known to play important roles in the activation and detoxification of carcinogens. Human CYP1A2 is involved in the metabolic activation of several carcinogens, i.e. aromatic and heterocyclic amines. Through the use of fluorometric high-throughput assays, the Km and Vmax values were obtained for the substrate 3-cyano-7-ethoyxyxoumarin. After optimizing the enzymes' assays, IC50 experiments were designed to study the differences between CYP1A1 and CYP1A2. Furafylline, resveratrol, letrozole, vorozole and ketoconazole, were tested for their inhibitory potency on these CYPs. Work in progress has shown furafylline and letrozole to be moderately potent inhibitors and resveratrol to be highly potent on CYP1A1. Furafylline was fairly potent on CYP1A2 while letrozole and vorozole were extremely weak inhibitors on CYP1A2. Future work will include the screening of the same drugs against rat CYP1A1 and CYP1A2 assays.

Use of fluorometric high-throughput screening assays to investigate the potency of a series of inhibitors on cytochrome P450 1A1 and 1A2

243rd National Meeting (2012)

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