Exten Industries (fka BB: EXTI)

[Patricia_1]

Email Response from Pfizer that was posted on RB

By: squiggstx
04 Mar 2004, 09:15 AM EST
Msg. 24202 of 24284
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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

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