Journal of Computer-Aided Molecular Design

, Volume 17, Issue 2, pp 119–127

In silico prediction of drug toxicity

  • John C. Dearden

DOI: 10.1023/A:1025361621494

Cite this article as:
Dearden, J.C. J Comput Aided Mol Des (2003) 17: 119. doi:10.1023/A:1025361621494


It is essential, in order to minimise expensive drug failures due to toxicity being found in late development or even in clinical trials, to determine potential toxicity problems as early as possible. In view of the large libraries of compounds now being handled by combinatorial chemistry and high-throughput screening, identification of putative toxicity is advisable even before synthesis. Thus the use of predictive toxicology is called for. A number of in silico approaches to toxicity prediction are discussed. Quantitative structure-activity relationships (QSARs), relating mostly to specific chemical classes, have long been used for this purpose, and exist for a wide range of toxicity endpoints. However, QSARs also exist for the prediction of toxicity of very diverse libraries, although often such QSARs are of the classification type; that is, they predict simply whether or not a compound is toxic, and do not give an indication of the level of toxicity. Examples are given of all of these. A number of expert systems are available for toxicity prediction, most of them covering a range of toxicity endpoints. Those discussed include TOPKAT, CASE, DEREK, HazardExpert, OncoLogic and COMPACT. Comparative tests of the ability of these systems to predict carcinogenicity show that improvement is still needed. The consensus approach is recommended, whereby the results from several prediction systems are pooled. It is simply amazing that we can formulate any kind of QSAR. The (desiredactivity) is only the starting point. The truly formidable problem is that oftoxicity, especially the difficult long-term toxicities resulting from chronicusage''. (Hansch & Leo [1])

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • John C. Dearden
    • 1
  1. 1.School of Pharmacy and ChemistryLiverpool John Moores UniversityLiverpoolEngland

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