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Metabolic Stability Assays

The metabolic stability assays provide a means to measure the rate of disappearance of a test compound over time in either microsomal or hepatocyte incubations, and these data are used to calculate intrinsic clearance. Microsomal assays primarily assess metabolism by the cytochrome P450 system (phase I enzymes) while hepatocyte assays more broadly assess the overall cellular metabolism of the test compound (phase I and phase II enzyme pathways). We provide metabolic stability assays for all small molecule formulations such as pharmaceuticals, industrial chemicals, and consumer products.

Our hepatocyte stability assays use a genetically modified version of the immortalized human liver cell line HepaRG™, created with our proprietary CompoZr® zinc finger nuclease (ZFN) technology. Apart from fresh human hepatocytes, HepaRG™ cells are the most metabolically active liver cell line described to date and have the potential for use as a viable surrogate in many functional liver assays, including metabolism and clearance testing, with none of the drawbacks of limited availability and donor-to-donor variation.

Liver metabolism is the major route for elimination for many drugs in humans and animals. The native ability of hepatic enzymes to metabolize a drug is commonly referred to as “intrinsic clearance” and is used to determine overall hepatic clearance, which takes into account additional factors such as hepatic blood flow and drug/protein binding.

Data from metabolic screening assays allow customers to identify metabolic liabilities early on and focus on the improvement of drug candidates through structure activity relationships.