Genotoxicity screening: the slow march to the future.
Genetic toxicology testing in drug discovery and development is slowly moving into the age of high-throughput screening (HTS). This has been helped by the development of new tools, as well as validation studies and data analysis to support their use in hit-to-lead or lead optimisation decisions. This review provides an overview of the current genetic toxicology methodologies and a few HTS methodologies. Comparisons are made between the predictivity of carcinogenesis that can be achieved in screening strategies as well as by the battery of regulatory tests. The importance of false-positive and false-negative calls at different stages in development is considered. There is a good prospect that in genetic toxicology, as in other areas of ADME-Tox, HTS will reduce the growing costs of carrying compounds with undesirable characteristics too far along the drug development process.
Walmsley
Richard M
RM
Faculty of Life Sciences, The University of Manchester, G10, Jackson's Mill, PO Box 88, Sackville Street, Manchester, M60 1QD, UK.
D000818:Animals; D015195:Drug Design; D005544:Forecasting; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods / Q000639:trends; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000639:trends