Exten Industries (fka BB: EXTI)

[Patricia_1]

Conferences/journals this year (9 and counting)

1. Jan 13, 2004 - Journal of Pharmacology and Experimental Therapeutics
http://intl-jpet.aspetjournals.org/cgi/content/abstract/jpet.103.061713v1

Induction of drug metabolizing enzymes and MDR1 using a novel hepatocyte cell line
Jessica B Mills 1, Kelly Rose 1, Nalini Sadagopan 1, Jasminder Sahi 1, Sonia M. F. de Morais 1*

1 Pfizer Global Research and Development

"Induction of drug metabolizing enzymes and transporters can cause drug-drug interactions and loss of efficacy. In vitro induction studies traditionally use primary hepatocyte cultures and enzyme activity with selected marker compounds. We investigated the use of a novel human hepatocyte clone, the Fa2N-4 cell line, as an alternative reagent, which is readily available and provides a consistent, reproducible system. We used the Invader® assay to monitor gene expression in these cells. This assay is a robust, yet simple, high-throughput system for quantification of mRNA transcripts. CYP1A2, CYP3A4, CYP2C9, UGT1A, and MDR1 transcripts were quantified from total RNA extracts from Fa2N-4 cells treated with a panel of known inducers and compared with vehicle controls. In addition, we used enzyme activity assays to monitor the induction of CYP1A2, CYP2C9, and CYP3A4. The Fa2N-4 cells responded in a similar manner as primary human hepatocytes. Treatment with 10 µM rifampin resulted in increases in CYP3A4 mRNA (17-fold) and activity (6-beta-hydroxytestoterone formation, 9-fold); and in CYP2C9 mRNA (4-fold) and activity (4'-hydroxydiclofenac formation, 2-fold). Treatment with 50 µM beta-naphthoflavone resulted in increases in CYP1A2 mRNA (15-fold) and activity (7-ethoxyresorufin O-dealkylation, 27-fold). UGT1A mRNA was induced by beta-naphthoflavone (2-fold), and MDR1 (P-glycoprotein) mRNA was induced by rifampin (3-fold). These preliminary data using a few prototypical inducers show that Fa2N-4 cells can be a reliable surrogate for primary human hepatocytes, and, when used in conjunction with the Invader® technology, could provide a reliable assay for assessment of induction of drug metabolizing enzymes and transporters."

2. 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

XenoTech will also sponsor an exhibit at this meeting.

3. IBC's Preclinical Development Forum
Feb 23 - 25, 2004
Cambridge, MA

XenoTech will sponsor an exhibit at this conference.

4. ISE's 4th International Conference on Early Toxicity Screening
Feb 23 - 24, 2004
San Diego, CA

Presentation by Dr. Andrew Parkinson, XenoTech CEO
Session 2
"Immortalized Hepatocytes: A New In Vitro Approach to Early Induction and Hepatotoxicity Screening

XenoTech will also sponsor an exhibit at this conference

5. ECPM Course: Toxicology and Clinical Pharmacology
March 8 - 10, 2004
Basel, Switzerland
Andrew Parkinson, Ph.D. will lecture on the topic of Drug Metabolism in Health and Disease.

6. 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

7. June 15, 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.

8. 7th International ISSX Meeting
August 29 - September 2, 2004
Vancouver, BC, Canada
Go to ISSX

9. AAPS (November 7 - 11, 2004)
http://www.aapspharmaceutica.com/meetings/annualmeet/am04/
XenoTech - booth 202 (at the main entrance)

Thanks goes to alandail on the RB EXTI thread.

http://www.ragingbull.lycos.com/mboard/boards.cgi?board=EXTI&read=21973