Immortalized Pig Hepatocytes: A Drug Discovery Model

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43CA096458-01
Agency Tracking Number: CA096458
Amount: $139,314.00
Phase: Phase I
Program: SBIR
Awards Year: 2003
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
MULTICELL TECHNOLOGIES, INC.
MULTICELL TECHNOLOGIES, INC., 55 ACCESS RD, STE 700, WARWICK, RI, 02886
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 RONALD FARIS
 (401) 738-7560
 FARIS@MULTICLTECHNOLOGIES.COM
Business Contact
Phone: (401) 738-7560
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): Drug-drug interactions can occur in a multiple drug regimen, where one drug interferes with the metabolism of another, leading to dangerous, unpredicted, and potentially fatal concentrations of medication. Unfortunately, a significant number of such drug interactions are first recognized during clinical trials. This nonrecognition of drug metabolic interactions is due in part to interspecies differences between rodents and man. A recent FDA report estimated that up to 20 percent of toxicity and potential drug interactions are misidentified in rat assays because of interspecies differences. Most drugs are metabolized by the hepatic cytochrome P450 enzymes, and a non-primate species most reflective of human CYP regulation is the pig. MultiCell Associates recently developed an immortalized porcine hepatocyte cell line designated HepLiu. The purpose of this Phase I project is to determine if HepLiu and its MSX resistant progeny, HL-MSX, can be employed as a screening bioassay to reproducibly detect inducers and inhibitors of human CYPs. This will be accomplished by assaying 24 compounds, whose effects on CYP3A4 and 1A activity have been well documented in humans. A positive correlation will provide the scientific basis for the long term goal of this project: to develop a predictive and economical assay based on the HepLiu porcine hepatocyte cell line, for screening the CYP induction and inhibition potential of new chemical entities in drug discovery.

* information listed above is at the time of submission.

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