CYP2C9 is a major cytochrome P450 enzyme that is involved in the metabolic clearance of various therapeutic agents. Disruption of this enzyme’s activity can lead to adverse drug reactions. Sulfaphenazole is an inhibitor of CYP2C9 (Ki = 0.3 μM) that demonstrates at least 100-fold selectivity over other CYP450 isoforms (Kis = 63 and 29 μM for CYP2C8 and CYP2C18, respectively, and no activity at CYP1A1, CYP1A2, CYP3A4, CYP2C19). At 10 μM, sulfaphenazole has been shown to inhibit endothelium-derived hyperpolarizing factor synthase, a CYP450 isozyme in the porcine coronary artery homologous to CYP2C8/9 that generates reactive oxygen species in coronary endothelial cells and modulates vascular tone and homeostasis.
