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Review
. 2010 Jun;14(3):308-14.
doi: 10.1016/j.cbpa.2010.02.001. Epub 2010 Mar 2.

Expanding the range of 'druggable' targets with natural product-based libraries: an academic perspective

Renato A Bauer  1 , Jacqueline M Wurst, Derek S Tan
Affiliations
Review

Expanding the range of 'druggable' targets with natural product-based libraries: an academic perspective

Renato A Bauer et al. Curr Opin Chem Biol. 2010 Jun.

Abstract

Existing drugs address a relatively narrow range of biological targets. As a result, libraries of drug-like molecules have proven ineffective against a variety of challenging targets, such as protein-protein interactions, nucleic acid complexes, and antibacterial modalities. In contrast, natural products are known to be effective at modulating such targets, and new libraries are being developed based on underrepresented scaffolds and regions of chemical space associated with natural products. This has led to several recent successes in identifying new chemical probes that address these challenging targets.

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Figures

Figure 1
Figure 1
Principal component analysis of 20 structural and physicochemical characteristics of 40 top-selling drugs (red circles), 60 natural products (blue triangles), including Ganesan’s rule-of-five compliant (pink filled) and non-compliant (blue filled) subsets, and 20 compounds from commercial drug-like libraries (ChemBridge, pink plusses; Chem Div, maroon crosses) illustrates the narrow focus of existing drugs and drug-like libraries in chemical space in contrast to natural products (see Supplementary Information for full details). The two unitless, orthogonal axes represent 73% of the information in the full 20-dimensional dataset. Recent examples of natural products and library-derived probes that address challenging targets discussed herein are also shown (green diamonds).
Figure 2
Figure 2
Small molecule inhibitors of protein–protein interaction targets.
Figure 3
Figure 3
Small molecule inhibitors of nucleic acid complexes.
Figure 4
Figure 4
New scaffolds that address antibacterial targets. The atropisomeric position in abyssomicin C is indicated with a *.
See this image and copyright information in PMC

References

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    1. Dobson CM. Chemical space and biology. Nature. 2004;432:824–828. • An excellent introduction to the concept of chemical space and its interactions with biology.

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