Expanding the medicinally relevant chemical space with compound libraries

Analysis of marketed drugs and commercial vendor libraries used in high-throughput screening suggests that the medicinally relevant chemical space may be expanded to unexplored regions. Novel regions of the chemical space can be conveniently explored with structurally unique molecules with increased complexity and balanced physicochemical properties. As a case study, we discuss the chemoinformatic profile of natural products in the Traditional Chinese Medicine (TCM) database and a large collection assembled from 30 small-molecule combinatorial libraries with emphasis on assessing molecular complexity. The herein surveyed combinatorial libraries have been successfully used over the past 20 years to identify novel bioactive compounds across different therapeutic areas. Combinatorial libraries and natural products are suitable sources to expand the traditional relevant medicinal chemistry space.

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► There is a need to explore novel regions of neglected chemical space.
► Molecules with increased complexity expand the medicinally relevant chemical space.
► Natural products and combinatorial libraries interrogate novel regions of chemical space.
► The Traditional Chinese Medicine has molecules more complex than commercial libraries.