In recent years, significant progress has been made in reducing metabolic instability due to cytochrome P450-mediated oxidation. High-throughput metabolic stability screening has enabled the advancement of compounds with little or no oxidative metabolism. In addition, high lipophilicity and low aqueous solubility of presently pursued chemotypes reduce the likelihood of renal excretion. Therefore, these low microsomal turnover compounds are generally substrates for non-CYP-mediated metabolism. Here, we focus on the utility of appropriate in vitro studies to characterize non-CYP-mediated metabolism and to understand the enzymes involved in pharmacokinetic studies in appropriately characterized surrogate species. We have developed a suite of validated in vitro assays using recombinant enzyme systems or cellular fractions with specific chemical inhibitors for phenotypic analysis of non-CYP metabolic pathways and assessment of DDI potential.
Creative Bioarray's non-CYP mediated metabolism services enable a greater understanding of which non-CYP enzymes might be involved in the metabolism of your compounds, or whether your compounds are inhibitors of non-CYP enzymes. These data can be used to determine potential drug-drug interactions. In addition, other enzymes can also be investigated upon request.