An Introduction to Drug Discovery

Fundamentals of Medicinal Chemistry, Edited by Gareth Thomas 

A more random approach to discovering a lead is the combinatorial chemistry approach (see Chapter 6). This uses a simultaneous multiple synthesis technique to produce large numbers of potential leads. These potential leads are subjected to rapid high throughput biological screening to identify the most active lead compounds. Once identified, these lead compounds are subject to further development. 

The selection of a lead compound and the development of a synthetic pathway for its preparation (see Chapters 10 and 11) is not the only consideration at the start of an investigation. Researchers must also devise suitable in vivo and in vitro tests to assess the activity and toxicity of the compounds produced. There is no point in carrying out an expensive synthetic procedure if at the end of the day it is impossible to test the product. 

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Debouck, C. Goodfellow, P. (1999). DNA microarrays in drug discovery and development. Nature Genet. 21, 48-50. Gabig, M. Wegrzyn, G. (2001). An introduction to DNA chips principles, technology, applications and analysis. Acta Biochim. Polon. 48(3), 615-622. 

Despite the failures of carbohydrate companies, the venture community should continue to fund the carbohydrate-based technologies and drug discovery efforts because there will be a significant return on investment. Also needed to continue the pace of product introduction is the application of a multi-disciplinary approach to drug discovery. An important factor for the success of carbohydrate-based therapeutics in the last decade is the combination of glycobiology and carbohydrate chemistry. 

After an introduction to basic principles, the book is divided into sections that cover industrial and regulatory applications, clinical applications, and research applications. A panel of experts provide extensive background for each subspeciality. Covering the many subdisciplines and providing pharmacokinetic concepts, terminology, and approaches. Pharmacokinetics in Drug Discovery and Development serves as a resource for professionals throughout this field. 

This chapter will concentrate on PET as a molecular imaging modality. An introduction to the technique will first be provided followed by specific examples where PET has been successfully used to obtain a better understanding of specific biological processes, in the detection of disease and also as a tool for drug discovery and development. 

Turner JR, Durham TA (2009) Integrated cardiac safety assessment methodologies for noncardiac drugs in discovery, development, and postmarketing surveillance. John Wiley Sons, Hoboken Turner JR (2010) New drug development an introduction to clinical trials, 2nd edn. Springer, New York... 

Walker, Sharon. Biotechnology Demystified. New York McGraw-Hill Professional, 2006. This is an introduction to the basics of and latest advances in molecular biology and tbe latest applications of these concepts to a range of discoveries, including new drugs and gene therapies. 

Chen J, Swamidass SJ, Dou Y, Bruand J, Baldi P (2005) ChemBD a public database of small molecules and related chemoinformatics resources. Bioinformatics 21 4133-4139 DrugBank http //www.drugbank.ca. Accessed 1 Feb 2014 WOMBAT http //www.sunsetmolecular.com/. Accessed 1 Feb 2014 MDDR http //accelrys.com/products/databases/bioactivity/mddr.html. Accessed 1 Feb 2014 Scior JT, Bernard P, Medina-Franco JL, Maggiora GM (2007) Large compound databases for structure-activity relationships studies in drug discovery. Mini Rev Med Chem 7 851-860 Leach AR, Gillet VJ (2003) An introduction to chemoinformatics. Kluwer Academic, Dordrecht... 

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