Skip to main navigation Skip to search Skip to main content

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

  • Sara E. Kearney
  • , Gergely Zahoránszky-Kohalmi
  • , Kyle R. Brimacombe
  • , Mark J. Henderson
  • , Caitlin Lynch
  • , Tongan Zhao
  • , Kanny K. Wan
  • , Zina Itkin
  • , Christopher Dillon
  • , Min Shen
  • , Dorian M. Cheff
  • , Tobie D. Lee
  • , Danielle Bougie
  • , Ken Cheng
  • , Nathan P. Coussens
  • , Dorjbal Dorjsuren
  • , Richard T. Eastman
  • , Ruili Huang
  • , Michael J. Iannotti
  • , Surendra Karavadhi
  • Carleen Klumpp-Thomas, Jacob S. Roth, Srilatha Sakamuru, Wei Sun, Steven A. Titus, Adam Yasgar, Ya Qin Zhang, Jinghua Zhao, Rodrigo B. Andrade, M. Kevin Brown, Noah Z. Burns, Jin K. Cha, Emily E. Mevers, Jon Clardy, Jason A. Clement, Peter A. Crooks, Gregory D. Cuny, Jake Ganor, Jesus Moreno, Lucas A. Morrill, Elias Picazo, Robert B. Susick, Neil K. Garg, Brian C. Goess, Robert B. Grossman, Chambers C. Hughes, Jeffrey N. Johnston, Madeleine M. Joullie, A. Douglas Kinghorn, David G.I. Kingston, Michael J. Krische, Ohyun Kwon, Thomas J. Maimone, Susruta Majumdar, Katherine N. Maloney, Enas Mohamed, Brian T. Murphy, Pavel Nagorny, David E. Olson, Larry E. Overman, Lauren E. Brown, John K. Snyder, John A. Porco, Fatima Rivas, Samir A. Ross, Richmond Sarpong, Indrajeet Sharma, Jared T. Shaw, Zhengren Xu, Ben Shen, Wei Shi, Corey R.J. Stephenson, Alyssa L. Verano, Derek S. Tan, Yi Tang, Richard E. Taylor, Regan J. Thomson, David A. Vosburg, Jimmy Wu, William M. Wuest, Armen Zakarian, Yufeng Zhang, Tianjing Ren, Zhong Zuo, James Inglese, Sam Michael, Anton Simeonov, Wei Zheng, Paul Shinn, Ajit Jadhav, Matthew B. Boxer, Matthew D. Hall, Menghang Xia, Rajarshi Guha, Jason M. Rohde

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish
Pages (from-to)1727-1741
Number of pages15
JournalACS Central Science
Volume4
Issue number12
DOIs
StatePublished - Dec 26 2018

Bibliographical note

Publisher Copyright:
© 2018 American Chemical Society.

Funding

NCATS thanks Dingyin Tao for assistance with compound characterization. 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). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Minister̀ e des Eaux et Forets).̂ O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce’s Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM-30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C. B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W. acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819).

FundersFunder number
Southwestern Oklahoma State Univ.
Sherman Fairchild Foundation
National Institutes of Health (NIH)
Camille and Henry Dreyfus Foundation
American Lebanese Syrian Associated Charities
National Center for Advancing Translational Sciences (NCATS)
John Stauffer Charitable Trust
Government of Madagascar
Arkansas Biosciences InstituteT32 CA062948-Gudas, R01GM121656
National Science Foundation Arctic Social Science Program1755698, 1725142, 5R01GM110131, 1665331, 1665145, 1464898, GM126221, 1414298, CHE-1665145, CHE-1725142, 1361173, CHE-0353662, 1463819, CHE-1005253
American Chemical Society Petroleum Research FundR15GM116032, CA78747, P30 GM103450, GM115575, 53767-ND1, GM114353, CA106150, CHE-1414298
National Center for Complementary and Integrative HealthU01 TW00313, 1 R01 AT008088
Fogarty International CenterTW009872
Christian Scholars FoundationCHE-1463819, CHE1755698, GM119426, RSG-13-011-01-CDD
American Cancer Society-Michigan Cancer Research FundCHE1361173, RSG-12-253-01-CDD
National Childhood Cancer Registry – National Cancer InstituteR01 CA158275
National Institute on AgingCHE-1464898, P01 AG012411, 213569
Office of the Assistant Secretary of Defense for Health AffairsR01-GM-30859, R0-1-NS-12389, P30 CA008748, W81XWH-17-1-0256, R01-HL25854, R01 GM111476
Arnold and Mabel Beckman FoundationGM 063557, GM 084333, P01CA125066
Pharmaceutical Research and Manufacturers of America FoundationGM129465, P41 GM076267
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical SciencesCHE-1665331, R01GM114061
Minister̀ e des Eaux et ForetsDA045884-01, R01GM071779, DA046487-01, AA026949-01, GM116952

    ASJC Scopus subject areas

    • General Chemistry
    • General Chemical Engineering

    Fingerprint

    Dive into the research topics of 'Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space'. Together they form a unique fingerprint.

    Cite this