By: squiggstx 04 Mar 2004, 09:15 AM EST Msg. 24202 of 24284 Jump to msg. # Response from Pfizer ---
Dear xxxxxxxx, Thank you for your interest in our publication. It is our opinion that the Fa2N-4 cells are the best clonal cell line available for CYP induction studies. They can be used to monitor multiple targets (CYP1A2, CYP2C9, CYP3A4, etc) and we are able to assess induction using either enzyme activity or messenger RNA. We have found that it responds to known inducers in a similar manner to primary hepatocytes. We feel the advantage of this system is that it is readily available and shows consistent performance, which isn't always the case with the primary hepatocytes due to their limited availability and donor-to-donor differences. Also, the system is cost-effective enough to utilize at earlier stages of Drug Discovery for those projects that may want to use induction data to drive SAR.
In addition to Pfizer, Hoffman-La Roche (Dr. Karl B. Frank) and Xenotech have produced induction data using the Fa2N-4 cells that is similar to our findings. We have not heard from anyone who has had negative results with the cell line. In fact, Xenotech is now distributing the cells commercially. We hope to see additional publications on this cell line from academics, as well as those in the pharmaceutical and biotechnology industries. Pfizer will be giving a couple of talks on the cell lines. I'll be speaking at CBI's Predictive ADME/Tox in Philadelphia on February 11th, and Dr. Sharon Ripp will be speaking at 7th International Conference on Drug-Drug Interactions in June in San Diego.
The level of CYP3A4 activity in the Fa2N-4 cells is lower than that seen in typical primary human hepatocytes, thus it may not be suitable for certain types of metabolism experiments (prediction of half-life, for example). The cells are being evaluated for various types of assays related to metabolism, transport, and toxicity within Pfizer, however we are not at liberty to discuss details at this time.
Induction is generally of less interest than inhibition DDIs. Thus, if this is the sole application for the cell line, it will have limited impact on the market for cryopreserved hepatocytes. If multiple applications are found for these cells, they could become a hot commodity for the pharmaceutical industry.
Best regards, ????????????? Scientist Pfizer Global Research & Development Groton Laboratories Building 118 West, Lab W122, Office xxxxx
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.