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.
Document Type
Article
Publication Date
12-5-2018
Digital Object Identifier (DOI)
https://doi.org/10.1021/acscentsci.8b00747
Funding Information
This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331).
Due to the large number of funding sources, only the first few are listed in this section. For the complete list of funding sources, please download this article.
Related Content
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscentsci.8b00747.
Repository Citation
Kearney, Sara E.; Zahoránszky-Kőhalmi, Gergely; Brimacombe, Kyle R.; Henderson, Mark J.; Lynch, Caitlin; Zhao, Tongan; Wan, Kanny K.; Itkin, Zina; Dillon, Christopher; Shen, Min; Cheff, Dorian M.; Lee, Tobie D.; Bougie, Danielle; Cheng, Ken; Coussens, Nathan P.; Dorjsuren, Dorjbal; Eastman, Richard T.; Huang, Ruili; Iannotti, Michael J.; Karavadhi, Surendra; Klumpp-Thomas, Carleen; Roth, Jacob S.; Sakamuru, Srilatha; Sun, Wei; Titus, Steven A.; Yasgar, Adam; Zhang, Ya-Qin; Zhao, Jinghua; Andrade, Rodrigo B.; Brown, M. Kevin; and Grossman, Robert B., "Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space" (2018). Chemistry Faculty Publications. 145.
https://uknowledge.uky.edu/chemistry_facpub/145
Supporting Information
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Chemistry Commons, Pharmacy and Pharmaceutical Sciences Commons
Notes/Citation Information
Published in ACS Central Science, v. 4, issue 12, p. 1727-1741.
Copyright © 2018 American Chemical Society
This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Due to the large number of authors, only the first 30 and the authors affiliated with the University of Kentucky are listed in the author section above. For the complete list of authors, please download this article or visit: https://doi.org/10.1021/acscentsci.8b00747