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Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space
Sara E Kearney1, Gergely Zahoránszky-Kőhalmi1, Kyle R Brimacombe1
1National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
ACS Central Science
|January 17, 2019
Summary
Natural products offer therapeutic potential but require extensive testing. The Canvass library, utilizing quantitative high-throughput screening (qHTS), efficiently evaluated numerous compounds for biological activity, identifying promising drug leads.
Area of Science:
- Natural Products Chemistry
- Chemical Biology
- Drug Discovery
Background:
- Natural products are a rich source of potential therapeutics.
- Limited resources often hinder biological evaluation of novel compounds.
- The Canvass library was created to facilitate screening of natural products.
Purpose of the Study:
- To establish and characterize the Canvass library for quantitative high-throughput screening (qHTS).
- To broadly survey the biological potential of natural products using automated screening.
- To identify novel bioactive compounds from natural sources.
Main Methods:
- Assembly of the Canvass library in collaboration with academic and industry partners.
- Quantitative high-throughput screening (qHTS) across diverse cell-based and biochemical assays.
- Analysis of assay data using quality control metrics, clustering, and promiscuity analyses.
Main Results:
- The Canvass library contains diverse structures with similarities to approved drugs.
- Screening identified compounds with significant biological activities.
- (-)-2(S)-cathafoline was found to stabilize endoplasmic reticulum calcium levels.
Conclusions:
- The Canvass library and qHTS workflow enable efficient biological surveying of natural products.
- This approach accelerates the identification of novel therapeutic leads.
- Natural products remain a vital resource for drug discovery.
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