Application Note: An In vitro Screening Method to Evaluate the Drug-Drug Interaction Due to Inhibition of Sulfotransferase Enzymes (SULTS)
2 June 2014
In this study, in vitro SULT inhibition assays were developed using human recombinant enzymes (SULT1A1, SULT1E1) and LC/MS/MS analysis as screening approaches to assess the impact of new chemical entities on altering the exposure of drugs metabolized by sulfotransferases. Using para-nitrophenol (PNP) as substrate, we evaluated protein and incubation time linearity, co-factor concentration effects, and enzyme kinetics (Km and Vmax). Using these optimized conditions, we then established an inhibition profile using quercetin, a known inhibitor of SULT enzymes. Early screening to identify the potential of a drug compound to inhibit SULT enzymes may be a useful tool for minimizing this type of drug-drug interaction in humans.