Design of chemical libraries for screening

Abstract

Importance of the field: The ultimate goal of discovery screening is to have a fast and cost-effective strategy to meet the demands of producing high-content lead series with improved prospects for clinical success. While high-throughput screening (HTS) dominates the drug discovery landscape, other processes and technologies have emerged, including high-content screening and fragment-based design to provide alternatives that may be more suitable for certain targets. There has been a growing interest in reducing the number of compounds to be screened to prevent the escalation in the costs, time and resources associated with HTS campaigns. Library design plays a central role in these efforts.

Areas covered in this review: This opinion provides a survey of some recent developments in the diversity based library design process, but within a historical context. In particular, the importance of chemotyping and substructure analysis and the challenges presented by novel lead discovery technologies that require the design of libraries for screening are discussed.

What the reader will gain: Readers will gain an appreciation of some developments in the field of library design and the factors that are driving the development of new library design technologies; specifically, challenges presented for chemoinformatics with the novel screening technologies in diversity based screening and compound filtering.

Take home message: Chemotyping and substrutural analysis are techniques that have been underutilized in the process of library design. However, they offer a direct way to evaluate libraries and have been successfully used to develop predictive methodologies. Tools are available to this end, but the full power of the approach has not been realized yet.

Keywords::

• cheminformatics
• chemotypes
• diversity based library design
• fragment based drug design
• virtual screening