title: Cheminformatic comparison of approved drugs from natural product versus synthetic origins.
abstract: Despite the recent decline of natural product discovery programs in the pharmaceutical industry, approximately half of all new drug approvals still trace their structural origins to a natural product. Herein, we use principal component analysis to compare the structural and physicochemical features of drugs from natural product-based versus completely synthetic origins that were approved between 1981 and 2010. Drugs based on natural product structures display greater chemical diversity and occupy larger regions of chemical space than drugs from completely synthetic origins. Notably, synthetic drugs based on natural product pharmacophores also exhibit lower hydrophobicity and greater stereochemical content than drugs from completely synthetic origins. These results illustrate that structural features found in natural products can be successfully incorporated into synthetic drugs, thereby increasing the chemical diversity available for small-molecule drug discovery.
authors.affiliation: Tri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 422, New York, NY 10065, USA.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Stratton
authors.affiliation: Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, PO Box B, Frederick, MD 21702, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Newman
authors.affiliation: Tri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 422, New York, NY 10065, USA; Chemical Biology Program and Tri-Institutional Research Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 422, New York, NY 10065, USA.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Tan
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry*; D017277:Drug Approval; D057927:Hydrophobic and Hydrophilic Interactions; D048088:Informatics; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D001688:Biological Products; D004364:Pharmaceutical Preparations
keywords: Cheminformatics; Natural products; Physicochemical properties; Principal component analysis; Synthetic drugs