Target families

Compounds were tested against related assays and showed activity, including selectivity within target families... 

Muller G. Medicinal chemistry of target family-directed masterkeys. Drug Discov Today 2003 8 681-91. 

Most drug discovery targets fit into one of the target families shown in Fig. 1. Included in the figure is the distribution of the market share by target family. 

FP assays can be developed for most of the target families. Examples of these assays are presented in the next section. 

Pin, J. P, Parmentier, M. L and Prezeau, L. (2001) Positive allosteric modulators for gamma-aminobutyric acidB receptors open new routes for the development of drugs targeting family 3 G protein-coupled receptors. Mol. Pharmacol. 60, 881-884. 

Notes Analysis (Joost and Methner, Genome Biol., 3(11) research 0063.1-0063.16,2002. http //genomebiology.com/ 2002/3/11 /research/0063). Profiling is performed in two phases. The first phase consists of a panel of 25 GPCR representing the families most commonly associated with off-target effects. Once a compound shows activity in one of the assays from the first set, full dose response is run on receptors within the same target family to assess selectivity (Phase 2). 

Protein target families are the fundamentals to build a framework for matching biological motifs with chemical scaffolds. Many structurally related targets find implications in different therapeutic areas, while exhibiting similar protein-ligand... 

D molecular interaction field analysis of their ligand binding sites target family landscapes. /. Med. Chem. 2002, 45, 2366-2378. 

Muller G. (2004) Target family-directed masterkeys in chemogenomics. In H Kubini, G Muller (eds), Chemogenomics in Drug Discovery—A Medicinal Chemistry Perspective, pp. 7-42. Wiley-VCH, Weinheim. 

Recent trends towards implementing chemogenomic strategies in drug discovery involve organizing research around target families in order to... 

Mestres J. (2005) Representativity of target families in the Protein Data Bank Impact for family-directed structure-based drug discovery. DrugDiscov. Today 10 1629-1637. http //cgl.imim.es/pdbrff/. 

At this point we have mainly considered recognition in terms of rules that apply across any target with defined geometry. Next, we consider how they can be derived within target families and how under these conditions it is possible to use the consistency within families to derive rules for the binding of fragments from experimental data even where structural definition is imprecise. 

In Chapter 5, Prof Didier Rognan from the University Louis Pasteur of Strasbourg elaborates on the basis of the GPCR target family, a concept for the in silico screening of the protein structure repertoire and of protein families in general. 

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