GPCR libraries

Wang, X.-C. and Saunders, J. GPCR library design. Book of Abstracts, 222nd ACS National Meeting, Chicago, 2001, MEDI-012. 

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). 

Serotonin 5HT2c agonist 13 Modeller FlexX 530 ChemDiv GPCR library, MW and pharmacophore filtered 5 12.8 lC5o = 20.1nM [25]... 

Table 3 delineates the libraries in from which GPCR inhibitors have been identified. The table is subdivided into several receptor classes opiate receptors (libraries 3.1-3.6), tachykinin receptors (libraries 3.7-3.12), endothelin A receptors (libraries 3.13-3.16) and other GPCRs (libraries 3.17-3,25). 

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. 

Savchuk, N.P., Tkachenko, S.E., and Baiakin, K.V. Rational design of GPCR-specific combinatorial libraries based on the concept of privileged substructures. In Chemoinformatics in... 

I 12 GPCR-specific Combinational Libraries Based on the Concept of Privileged Substructures... 

In general, reagent-based selection is much faster and more convenient to execute in the laboratory as compared with the product-based selection. On the other hand, the latter strategy usually provides more accurate results. There exists a potential to combine both approaches to achieve more optimal results, particularly in the case of large exploratory virtual combinatorial libraries, for which mass random synthesis and screening are not economically feasible. In this article, we demonstrated the usefulness of property-based approach for selection of optimal GPCR ligands. 

S. A., Okun, L, Ivashchenko, A.A., and Savchuk, N.P. Property-based design of GPCR-targeted library./. Chem. Inf. Comput. Sci. 2002, 42, 1332-1342. 

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