Cytochrome P450 enzymes are members of one of the most relevant families of drug metabolizing enzymes. They are highly expressed in the liver, but also occur in other organs and tissues, such as the gastrointestinal tract and the kidneys.
The inhibition of CYP enzymes can impact the metabolism of co-administered drugs. As a consequence, increased plasma levels and associated adverse events may arise. The severity of this drug–drug interaction depends on the potency of the inhibition as well as on its mechanism (i.e., reversible or irreversible inhibition).
Our CYP inhibition laboratory is equipped with state-of-the-art equipment to offer a high-throughput screening assay for all major CYP enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4/5). In our human liver microsome (hLM) assay, we incubate CYP-isoform-specific substrates in the presence of different test compound concentrations. The metabolite formation is determined using LC-MS/MS bioanalysis and compared to a solvent control. The concentration of test compound that results in 50% inhibition (IC50) of the isoform-specific transformation is reported. Depending on your needs, the assay can be performed with or without a pre-incubation period to investigate the time dependency of the inhibition.
For a more profound understanding of time-dependent inhibitory effects, we offer additional assays for the investigation of mechanism-based inhibition (MBI) on CYP3A4. In our high-throughput screening MBI, a variety of test compound concentrations are incubated in hLM with and without one fixed pre-incubation period. As a result, a screening-level inhibitory constant (Ki) and kinact are derived. A similar manual assay is available that applies multiple pre-incubation periods to evaluate a comprehensive Ki and kinact.
We understand the importance of investigating CYP inhibition in drug discovery, and we are committed to providing you with the best service possible. Our dedicated team of scientists works closely with you to make the most of your study and help you achieve your research goals.