Replies to post #100 on Exten Industries (fka BB: EXTI)

[Patricia_1]

Pfizer/XenoTech/Upcoming Conferences..presenting EXTI's cell lines at multiple conferences this year.

Feb 11, 2004 - Annual Forum on ADME/Tox

http://www.cbinet.com/events/HB405/day_one.html

2:15 Induction of Major Cytochrome P450 Enzymes in Immortalized Human Hepatocytes
Primary cultures of human hepatocytes are the most suitable test system to evaluate induction of drug metabolizing enzymes by New Chemical Entities (NCEs). The supply of human livers available for support of drug development though is increasingly limited and their response to NCE’s is highly variable due to numerous environmental and genetic factors. Recently, SV40 T Ag-immortalized hepatocytes, Fa2N-4, demonstrated cytochrome P450 (CYP) enzyme’s activity and inducibility, among other characteristics of differentiated liver functions. Since these cells can be cryopreserved and are readily available, they constitute a test system alternative to primary cultures of hepatocytes. This session discusses the data from two independent laboratories who have characterized the activity of multiple CYP in response to prototypical enzyme inducers, which regulate gene expression through distinctive nuclear receptor pathways.
• Cultured with a uniquely formulated media, these cells grow and maintain their functions in 96-well plates
• Cell culture and LC/MS/MS methods were developed to ascertain inductive potential of NCEs with Fa2N-4 cells

Jessica B. Mills, Ph.D., Associate Scientist, Pfizer Inc
Andrew Parkinson, Ph.D., President and CEO, XenoTech LLC


Wednesday, March 24, 2004 Society of Toxicology Annual Meeting

http://www.toxicology.org/memberservices/meetings/am2004/

1:30 - 4:30 p.m. - THE USE OF IMMORTALIZED HEPATOCYTES IN METABOLISM AND INDUCTION STUDIES
Kevin C. Lyon, XenoTech

June15 2004- 7th International Conference on Drug-Drug Interactions

https://www.isciencex.com/DDI-2004%20program%20FINAL.htm

10:30 AM – 11:15 AM
Immortalized and Fresh Human Hepatocytes: Use and Performance in Metabolism, Induction and Toxicity Screening (Andrew Parkinson, XenoTech, Lenexa, KS) Human hepatocytes play several key roles in preclinical drug development, including assessment of enzyme induction, cellular toxicity, drug metabolism and species comparisons. This presentation compares fresh and cryopreserved human hepatocytes to a new human hepatocyte cell line that has the potential to solve the problem of supply and variability that restrict the use of human hepatocytes for enzyme induction and other in vitro screening.

11:15 AM – 12:00 PM

Predicting Clinical DDI Arising from CYP3A4 Induction Using In Vitro Data: Studies with the Fa2N-4 Immortalized Hepatocyte Line (Sharon L. Ripp, Pfizer Global Research & Development; Groton, CT) The Fa2N-4 human hepatocyte line, when treated with prototypical inducers, shows a robust induction of CYP3A4 mRNA and enzymatic activity. We are examining ways to use this in vitro induction data to predict clinical DDI due to CYP3A4. One possibility is to combine potency and efficacy data from Fa2N-4 cells with efficacious plasma concentrations to assess in vivo induction potential. Studies assessing the validity of this approach using prototypical inducers will be discussed.