Liver toxicity is a major cause of drug failure in clinical trials and often leads to the complete market withdrawal of many approved drugs today. Due to inherent differences in drug metabolism between species, it’s also difficult to extrapolate results obtained from preclinical animal models for human use. But new research on upcyte® hepatocytes suggests that they may be an effective solution for reducing attrition due to metabolism-mediated toxicity and the key to improving the safety of new drug candidates.
upcyte® cells are proliferating human hepatocytes, or parenchymal liver cells, that retain important drug metabolizing enzymes, such as cytochrome P450 3A4 (CYP3A4). These enzymes make upcyte® cells a valuable model system to examine drug-induced liver injury (DILI).
In a recent study by INDIGO Biosciences, researchers examined the cytotoxicity present in upcyte® cells from four different donors for twelve compounds, exploring the utility of upcyte® cells for screening compounds for hepatotoxicity and the rapid assessment of variability in humans for hepatotoxic responses.
These compounds included:
The research aimed to contribute new insights on the use of upcyte® hepatocytes as an effective method of studying drug-induced liver injury, which would not bring with it the challenge of informing human results from that of preclinical animal models. Researchers assessed the utility of assay-ready upcyte® hepatocytes to conduct rapid assessments of cytotoxicity by model hepatotoxicants, compare the four upcyte® hepatocyte lines to study donor-to-donor variability, and utilize specific cytochrome P450 inhibitors to determine the potential bioactivation of model hepatotoxicants in human upcyte® hepatocytes.
The study drew several conclusions about the use of upcyte® cells in DILI studies. It found that upcyte® hepatocytes are sensitive to a variety of known hepatotoxicants, including hepatotoxicants that require bioactivation. It revealed new insights on the ability of upcyte® cells to screen compounds for hepatotoxicity and bioactivate compounds using cytochrome P450 inhibitors. The results also support the viability of using upcyte® cells to reduce attrition due to metabolism-mediated toxicity and to improve the safety of new drug candidates.
For those interested in exploring this study in more detail, a free scientific poster from INDIGO Biosciences offers information on the study’s materials and methods, data and findings, and key conclusions. Download this informative resource today to learn more about drug-induced liver injury in upcyte® hepatocytes and enhance your own research.
Do you still have questions about this subject? Request information from the team at INDIGO Biosciences to learn more, explore related testing and request custom research studies.