GPCR focused library

Barbosa, F., Mao, B., Revah, F. and Froloff, N. (2005) QSAR strategy and experimental validation for the development of a GPCR focused library. QSAR and Combinatorial Science, 24, 508-516. 

Jimonet, P. and Jager, R. (2004) Strategies for designing GPCR-focused libraries and screening sets. Current Opinion in Drug Discovery el Development, 7, 325-333. 

Using such a table, it is then possible to sort a whole family of GPCRs according to the type of SAR that the receptor displays. This can, in turn, be used to design focused libraries with which to screen particular subsets of receptors (see below), or to define search criteria with which to trawl... 

In the technique of post hoc design, a set of descriptors are built up by examination of a set of compounds active at a particular receptor family or sub-class. Normally, the set of drugs would be from a commercial database such as MDDR or the Merck Index, etc. and the descriptors would usually be substructural fragment or key based. One example would be the GPCR-PA+ sub-class referred to above, where BCUT descriptors have been used to aid the design of a focused library of aroimd 2000 compoimds based on 8 scaffolds. Libraries have also been constructed based on peptidomimetic principles as well as on the concepts of privileged structures. ... 

Bissantz, C., Schalon, C., Cuba, W., and Stahl. M. (2005) Focused library design in GPCR projects on the example of 5-HT (2c) agonists comparison of structure-based virtual screening with ligand-based search methods. Proteins, 61, 938—952. 

There are a number of approaches to the design of libraries of compounds focused on GPCRs and such libraries fall into a number of classes depending on how they have been designed. 

There are three major sources for a typical corporate compound collection project-specific compounds accumulated over a long period of time through medicinal chemistry efforts for various therapeutic projects, individual compounds from commercial sources, and compounds from combinatorial chemistry. In practice, compound collections are often divided into subsets, for example, the diverse subsets for general HTS and target-focused subsets (such as kinase libraries or GPCR libraries). For library design, diversity and similarity are generally built into the libraries of compounds to be synthesized and/or purchased (73). 

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