Irwin screen

Generally, groups of four rodents or four nonrodents per data point should be adequate, except in the case of a free-standing Irwin screen or functional observational battery (FOB), where many endpoints are assessed in the same animal (with high variability associated with individual endpoints). Here the animals of one sex would be advisable. 

Irwin, J. J., Shoichet, B. K. ZINC - a free database of commercially available compounds for virtual screening. J. 

Irwin, S. (1962). Drug screening and evaluative procedures. Science 136 123-128. 

The front end of this tier approach is a screen, the functional observation battery (FOB) Gad (1982) or Irwin (1968) screen. This is the tool of choice for initial (and for most of the compounds covered by this volume, the only screen tests for) identification of potentially neurotoxic chemicals. The use of such screens, other behavioural test methods, or what are generally called clinical observations does, however, warrant one major caution or consideration. That is that short-term (within 24 hr of dosing or exposure) observations are insufficient on their own to differentiate between pharmacologic (reversible in the short term) and toxicological (irreversible) effects. 

Irwin, S. (1964). Drug screening and evaluation of new compounds in animals. Animal and clinical pharmacologic techniques. In Drug Evaluation. Nodine, J. and Sieger, P. (Eds.) "Year Book Medical Publishers, Inc., Chicago, pp. 26-54. 

J.J. Irwin, How good is your screening library , Curr. Opin. Chem. Biol., 10, 352-356 (2006). 

Kolb P, Ferreira RS, Irwin JJ, Shoichet BK (2009) Docking and chemoinformatic screens... 

O Brien PJ, Irwin W, Diaz D, Howard-Cofield E, Krejsa CM, Slaughter MR, et al. High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high content screening. Arch Toxicol 2006 80 580-604. 

ZINC (Irwin and Shoichet, 2005) is a freely accessible database of increasing use in virtual screening and other computational applications. ZINC contains over 8 million purchasable compounds and it is a very attractive source of compounds to perform chemoinformatic comparisons with other collections. 

Babaoglu K, Simeonov A, Irwin JJ et al (2008) Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase. J Med Chem 51 2502-2511... 

Hert, J., Irwin, J.J., Laggner, C., Reiser, M.J., and Shoichet, B.K. (2009) Quantifying biogenic bias in screening libraries. Nature Chemical Biology, 5, 479-483. 

Irwin, J.J. (2006) How good is your screening library Current Opinion in Chemical Biology, 10, 352—356. 

Irwin, J.J. (2008) Community benchmarks for virtual screening. Journal of Computer-Aided Molecular Design, 22, 193-199. 

Huang, N., Kalyanaraman, C., Irwin, J.J., and Jacobson, M.P. (2006) Physics-based scoring of protein-ligand complexes enrichment of known inhibitors in large-scale virtual screening. Journal of Chemical Information and Modeling, 46, 243-253. 

Fan, H., Irwin, J.J.,Webb, B.M., Klebe, G., Shoichet, B.K., and Sali, A. (2009) Molecular docking screens using comparative models of proteins. Journal of Chemical Information and Modeling, 49, 2512-2527. 

Tuccinardi, T. (2009) Docking-based virtual screening recent developments. Combinatorial Chemistry ei High Throughput Screening, 12 (3), 303-314. Fan, H Irwin, J.J., Webb, B.M., Klebe,... 

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