Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space

• Type of Material: Article
• Authors: Sara E. Kearney, National Institutes of Health; Gergely Zahoranszky-Kohalmi, National Institutes of Health; Kyle R. Brimacombe, National Institutes of Health; Mark J. Henderson, National Institutes of Health; Caitlin Lynch, National Institutes of Health; Tongan Zhao, National Institutes of Health; Kanny K. Wan, National Institutes of Health; Zina Itkin, National Institutes of Health; Christopher Dillon, National Institutes of Health; Min Shen, National Institutes of Health; Dorian M. Cheff, National Institutes of Health; Tobie D. Lee, National Institutes of Health; Danielle Bougie, National Institutes of Health; Ken Cheng, National Institutes of Health; Nathan P. Coussens, National Institutes of Health; Dorjbal Dorjsuren, National Institutes of Health; Richard T. Eastman, National Institutes of Health; Ruili Huang, National Institutes of Health; Michael J. Iannotti, National Institutes of Health; William Wuest, Emory University
• Language: English
• Date: 2018-12-26
• Publisher: American Chemical Society: Open Access Titles
• Publication Version: Final Published Version
• Copyright Statement: © 2018 American Chemical Society.
• Final Published Version (URL): http://dx.doi.org/10.1021/acscentsci.8b00747
• Title of Journal or Parent Work: ACS Central Science
• ISSN: 2374-7943
• Volume: 4
• Issue: 12
• Start Page: 1727
• End Page: 1741
• Grant/Funding Information: See publication for full funding statement.
• Keywords: CONSTITUTIVE ANDROSTANE RECEPTOR; Chemistry, Multidisciplinary; Chemistry; DISCOVERY; DRUGS; Physical Sciences; Science & Technology; IDENTIFICATION
• Research Categories: Chemistry, Biochemistry; Health Sciences, Pharmacology; Biology, Molecular

Abstract

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (-)-2(S)-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening.