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The Predictive Nature of High-Throughput Toxicity Screening
Using a Human Hepatocyte Cell Line
by Norman L. Sussman, M.D.1, Monika Waltershield,
M.S.1, Terolyn Bulter, M.S.1, James J. Cali Ph.D.2,
Terry Riss, Ph.D.2, and James H. Kelly, Ph.D.1
1Amphioxus Cell Technologies, 2Promega Corporation
Drug discovery has become an industrialized process in which vast libraries
of compounds are screened for activity against a chosen target. The wealth of
active compounds that emerge from these primary screens has created a bottleneck
in drug development. First-round hits do not often meet the safety and efficacy
criteria required for human therapeutics, so sequential rounds of optimization
are required before a product can be administered to humans. Optimization
requires assays that test Absorption, Distribution, Metabolism, Elimination and
Toxicity. In this paper we demonstrate the utility of high-throughput testing in
a human liver cell line. If the technologies and reagents presented in this
article had been available earlier, ADME/Tox screening could have prevented
deaths and costly drug recalls by two major pharmaceutical companies.
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