Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?
Year: 2015
Type: review
Abstract: High-throughput biology has contributed a wealth of data on chemicals, including natural products (NPs). Recently, attention was drawn to certain, predominantly synthetic, compounds that are responsible for disproportionate percentages of hits but are false actives. Spurious bioassay interference led to their designation as pan-assay interference compounds (PAINS). NPs lack comparable scrutiny, which this study aims to rectify. Systematic mining of 80+ years of the phytochemistry and biology literature, using the NAPRALERT database, revealed that only 39 compounds represent the NPs most reported by occurrence, activity, and distinct activity. Over 50% are not explained by phenomena known for synthetic libraries, and all had manifold ascribed bioactivities, designating them as invalid metabolic panaceas (IMPs). Cumulative distributions of ∼200,000 NPs uncovered that NP research follows power-law characteristics typical for behavioral phenomena. Projection into occurrence-bioactivity-effort space produces the hyperbolic black hole of NPs, where IMPs populate the high-effort base.
Source: Journal of Medicinal Chemistry
Institutions: University of Illinois Chicago, Dominican University
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: Office of Dietary Supplements, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine, National Institute of Dental and Craniofacial Research, National Center for Complementary and Integrative Health
Awards: Multidisciplinary Oral Science Training, Biomodification of Dentin Matrix Structure, Automated technology for purification of active ingredients in natural products, Center for Natural Product Technologies at UIC (CeNAPT), G399164058, EVALUATION OF ALASKAN PLANTS FOR TUBERCULOSIS TREATMENT, Development of a transformative approach to the rapid detection, isolation, and i, G7051389588, Spectrometric Validation of Botanical Materials and Reference Standards, Botanical Dietary Supplements for Women's Health, G9000328690, Research Training in Natural Product Complementary and Integrative Health
OpenAlex ID: W2234844573