        |
|
 MultiCell's immortalized human hepatocytes, when used in combination with our serum-free MFE™ culture medium, are the ideal liver cells to reliably predict CYP induction and hepatotoxicity. A fundamental understanding of how the body metabolizes and reacts to drugs will lead to the creation of safer and more effective medicines. Cytochrome P450s (CYPs) are a family of phase I liver enzymes that catalyze the primary metabolism of most drugs. CYP3A4 is responsible for the metabolism of at least 40% of all ingested drugs. Pharmacological induction of CYPs and related drug metabolizing enzymes often leads to drug-drug interactions and/or altered metabolism and clearance of the drug itself. MultiCell's immortalized human hepatocyte cell lines, designated Ea1C-35 and Fa2N-4, continue to express multiple inducible CYPs, including CYPs 1A2, 2B6, 2C9 and 3A4. These cell lines, when used in combination with our serum-free MFE™ culture medium, are ideal predictive hepatotoxicity models to screen new drug entities and lead compounds for their impact upon CYP induction using high throughput assays. MultiCell's immortalized human hepatocyte cell line, designated Fa2N-4, continues to express multiple forms of cytochrome P450 that are pharmacologically inducible when grown in 24-96 well formats.
MultiCell's immortalized Fa2N-4 human hepatocyte cell line can be used in high throughput assays to reproducibly identify and rank CYP1A2 and CYP3A4 enzyme inducers.
MultiCell's immortalized human hepatocyte cell lines proliferate easily in culture and retain hepatic function. Alternative sources of human hepatocytes are limited in supply and variable in quality. Cell lines derived from liver tumors are too poorly differentiated, lacking liver-specific expression, to be suitable for therapeutic and diagnostic applications. Early identification of potential toxicities will enable pharmaceutical companies to eliminate potential compound failures long in advance of clinical trials. Our cell products can significantly reduce costs associated with drug discovery as well as improve safety and efficacy of new medicines. Results from independent studies indicate that MultiCell's proliferating Fa2N-4 immortalized human hepatocytes can be used to predictably measure hepatotoxicity. Treatment of cells with toxic concentrations of several agents (i.e. 3-methylchloanthrene, methotrexate, menadione, rotenone and troglitazone) caused loss of membrane integrity and release of alpha-glutathione-S-transferase into culture media. In contrast, little or no enzyme was released when Fa2N-4 cells were treated with nontoxic concentrations of omeprazole, acetaminophen, probencid, felbamate or rifampin. For more details see Publications.
|
