Target-focused libraries

The selection of compounds for an NMR screening library is dictated by its intended purpose. There are four basic types of libraries general screening, targeted, focused, and follow-up. 

More recently, the focus has moved from diversity in favor of combinatorial libraries designed to target specific receptors or enzymes (12). While these single-target-focused libraries remain a key component of many drug-discovery programs, and are useful in both hit to lead and lead optimization contexts,... 

Computational models relating molecular structure and/or properties to biological activity are required for the design of both target-focused and target class combinatorial libraries based on known active ligands. These models are developed from descriptors, which encode information about molecular properties... 

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). 

Since the most favourable chemical fragment space for any given class of targets varies over time, we recommend planning ahead for dynamic library extensions, which may comprise target-focused fragments, new chemistries, new privileged chemical classes or... 

Key Words Chemical diversity compound design diversity-oriented synthesis druglike compounds molecular properties natural products rule of five structure-activity relationship target-focused compound libraries. 

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