Cheminformatic analysis of natural product-based drugs and chemical probes Journal Article

Authors: Stone, S.; Newman, D. J.; Colletti, S. L.; Tan, D. S.
Article Title: Cheminformatic analysis of natural product-based drugs and chemical probes
Abstract: Covering: 1981 to 2019 Natural products continue to play a major role in drug discovery, with half of new chemical entities based structurally on a natural product. Herein, we report a cheminformatic analysis of the structural and physicochemical properties of natural product-based drugs in comparison to top-selling brand-name synthetic drugs, and a selection of chemical probes recently discovered from diversity-oriented synthesis libraries. In this analysis, natural product-based drugs covered a broad range of chemical space based on size, polarity, and three-dimensional structure. Natural product-based structures were also more prevalent in top-selling drugs of 2018 compared to 2006. Further, the drugs clustered well according to biosynthetic origins, but less so based on therapeutic classes. Macrocycles occupied distinctive and relatively underpopulated regions of chemical space, while chemical probes largely overlapped with synthetic drugs. This analysis highlights the continued opportunities to leverage natural products and their pharmacophores in modern drug discovery.
Keywords: design; macrocycles; small molecules; diversity-oriented synthesis; discovery; distributions; oral bioavailability; aqueous solubility
Journal Title: Natural Product Reports
Volume: 39
Issue: 1
ISSN: 0265-0568
Publisher: Royal Society of Chemistry  
Date Published: 2022-01-19
Start Page: 20
End Page: 32
Language: English
ACCESSION: WOS:000680463400001
DOI: 10.1039/d1np00039j
PMCID: PMC8792152
PUBMED: 34342327
Notes: Review -- Source: Wos
Citation Impact
MSK Authors
  1. Derek S Tan
    81 Tan
  2. Samantha Stone
    1 Stone