THE PREDICTIVE NATURE OF HIGH-THROUGHPUT TOXICITY SCREENING USING A HUMAN HEPATOCYTE CELL LINE
Norman Sussman, Monika Waltershied, Terolyn Butler, James J. Cali, Terry Riss, James H. Kelly · 2002
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. Firstround 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 (ADME/Tox). 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.