Drugs (XENObiotics) are predominantly metabolized in the liver. The cytochrome P450 family (CYP) is involved in the oxidative (phase I) metabolism. In the second phase, these metabolites are modified by glucuronosyl- and sulfotransferases (phase II enzymes). Finally they are actively eliminated by transporters (phase III). These proteins significantly affect the bioavailability of drugs. Hence, new substances need to be tested for their potential to induce such enzymes and transporters. The FDA recommends using mRNA profiling to assess the induction of cytochrome P450 in preclinical studies.
However, SIGNATOPE offers protein-based assays, because protein levels have a higher predictive value. Our SIGNAXENO assays allow to measure 100s of samples per week, using less than 20 µg of human hepatocyte material. This is a 50-fold improvement in sample throughput and tissue usage compared to other methods.
Currently we have established assays for Cytochrome P450 isoforms 1A1, 1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2E1, 2D6, 3A4, 3A5, 3A7 and CPR.