Abstract
Mounting pressures in pharmaceutical research necessitate ever increasing efficiency to lower cost and produce results. This is especially true in the realm of high-throughput screening (HTS) where large pharmaceutical companies historically test many hundreds of thousands of compounds in the search for new drug leads. As a result of this pressure the old mantra of “screen them all” is rapidly becoming a phrase of the past and the search for new, more efficient methods for discovering leads begins. This chapter will describe some of the methods, techniques, and strategies that have been implemented at Pharmacia that attempt to identify compounds that are likely to provide the most useful information so that one might discover solid leads rapidly.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Drews, J. (2003) Strategic trends in the drug industry. Drug Disc. Today 8, 411–420.
Lajiness, M. S. and Maggiora, G. M. (2004) How consistent are medicinal chemists in reviewing lists of compounds (manuscript in preparation).
Lipinski, C. A., Lombardo, F., Dominy, B. W., and Feeney, P. J. (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug. Del. Rev. 23, 3–25.
Roche, O., Schneider, P., Zuegge, J., et al. (2002) Development of a virtual screening method for identification of “frequent hitters” in compound libraries. J. Med. Chem. 45, 137–142.
Rishton, G. M. (1997) Reactive compounds and in vitro false positives in HTS. Drug Disc. Today 2, 382–384.
Bikker, J. A., Dunbar, J. B., Bornemeier, D., Wild, D. J., Calvet, A., and Humblet, C. (2001) Needles in hayfields: strategies for rapid HTS triage analysis. Abstracts of Papers of the ACS, 222, 50-CINF, Part 1 Aug 2001.
Muegge, I. (2003) Selection criteria for drug-like compounds. Med. Res. Rev. 23, 302–321.
Egan, W. J., Walters, W. P., and Murcko, M. A. (2002) Guiding molecules towards drug-likeness. Curr. Opin. Drug. Disc. Des. 5, 540–549.
Rishton, G. M. (2003) Nonleadlikeness and leadlikeness in biochemical screening. Drug Disc. Today 8, 86–96.
Charifson, P. S. and Walters, W. P. (2002) Filtering databases and chemical libraries. J. Comput.-Aided Mol. Design 16, 311–323.
Oprea, T. I. (2002) Current trends in lead discovery: Are we looking for the appropriate properties? J. Comput.-Aided Mol. Design 16, 325–334.
Matter, H., Baringhaus, K. H., Naumann, T., Klabunde, T., and Pirard, B. (2001) Computational approaches towards the rational design of drug-like compound libraries. Comb. Chem. HTS 4, 453–475.
McGovern, S. L., Caselli, E., Grigorieff, N., and Shoichet, B. K. (2002) A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J. Med. Chem. 45, 1712–1722.
McGovern, S. L. and Shoichet, B. K. (2003) Kinase inhibitors: not just for kinases anymore. J. Med. Chem. 46, 1478–1483.
McGovern, S. L., Helfand, B., Feng, B., and Shoichet, B. K. (2003) A specific mechanism for nonspecific inhibition. J. Med. Chem. 46, 4265–4272.
Seidler, J., McGovern, S. L., Doman, T. N., and Shoichet, B. K. (2003) Indentification and prediction of promiscuous aggregating inhibitors among known drugs. J. Med. Chem. 46, 4477–4486.
Whitlock, H. W. (1998) On the structure of total synthesis of complex natural products. J. Org. Chem. 63, 7982–7989.
Barone, R. and Channon, M. (2001) A new and simple approach to chemical complexity. Application to the synthesis of natural products. JCICS 41, 269–272.
Gao, H., Shanmugasundaram, V., and Lee, P. H. (2002) Estimation of aqueous solubility of organic compounds with QSPR approach. Pharm. Res. 19, 497–503.
Lajiness, M. S. (1997) Dissimilarity-based compound selection techniques. Perspect. Drug Disc. Design 7/8, 65–84.
Hagadone, T. R. and Lajiness, M. S. (1993) Integrating chemical structures into an extended relational database system. Proceedings of the 2nd international chemical structures in chemistry conference. Warr, W. (ed.), Springer, Berlin, Germany, pp. 257–269.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Humana Press Inc.
About this protocol
Cite this protocol
Lajiness, M.S., Shanmugasundaram, V. (2004). Strategies for the Identification and Generation of Informative Compound Sets. In: Bajorath, J. (eds) Chemoinformatics. Methods in Molecular Biology™, vol 275. Humana Press. https://doi.org/10.1385/1-59259-802-1:111
Download citation
DOI: https://doi.org/10.1385/1-59259-802-1:111
Publisher Name: Humana Press
Print ISBN: 978-1-58829-261-2
Online ISBN: 978-1-59259-802-1
eBook Packages: Springer Protocols