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 language | English (US) |
---|---|
Pages (from-to) | 1727-1741 |
Number of pages | 15 |
Journal | ACS Central Science |
Volume | 4 |
Issue number | 12 |
DOIs | |
State | Published - Dec 26 2018 |
ASJC Scopus subject areas
- Chemistry(all)
- Chemical Engineering(all)
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Canvass : A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space. / Kearney, Sara E.; Zahoránszky-Kohalmi, 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; Burns, Noah Z.; Cha, Jin K.; Mevers, Emily E.; Clardy, Jon; Clement, Jason A.; Crooks, Peter A.; Cuny, Gregory D.; Ganor, Jake; Moreno, Jesus; Morrill, Lucas A.; Picazo, Elias; Susick, Robert B.; Garg, Neil K.; Goess, Brian C.; Grossman, Robert B.; Hughes, Chambers C.; Johnston, Jeffrey N.; Joullie, Madeleine M.; Kinghorn, A. Douglas; Kingston, David G.I.; Krische, Michael J.; Kwon, Ohyun; Maimone, Thomas J.; Majumdar, Susruta; Maloney, Katherine N.; Mohamed, Enas; Murphy, Brian T.; Nagorny, Pavel; Olson, David E.; Overman, Larry E.; Brown, Lauren E.; Snyder, John K.; Porco, John A.; Rivas, Fatima; Ross, Samir A.; Sarpong, Richmond; Sharma, Indrajeet; Shaw, Jared T.; Xu, Zhengren; Shen, Ben; Shi, Wei; Stephenson, Corey R.J.; Verano, Alyssa L.; Tan, Derek S.; Tang, Yi; Taylor, Richard E.; Thomson, Regan J.; Vosburg, David A.; Wu, Jimmy; Wuest, William M.; Zakarian, Armen; Zhang, Yufeng; Ren, Tianjing; Zuo, Zhong; Inglese, James; Michael, Sam; Simeonov, Anton; Zheng, Wei; Shinn, Paul; Jadhav, Ajit; Boxer, Matthew B.; Hall, Matthew D.; Xia, Menghang; Guha, Rajarshi; Rohde, Jason M.
In: ACS Central Science, Vol. 4, No. 12, 26.12.2018, p. 1727-1741.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Canvass
T2 - A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space
AU - Kearney, Sara E.
AU - Zahoránszky-Kohalmi, Gergely
AU - Brimacombe, Kyle R.
AU - Henderson, Mark J.
AU - Lynch, Caitlin
AU - Zhao, Tongan
AU - Wan, Kanny K.
AU - Itkin, Zina
AU - Dillon, Christopher
AU - Shen, Min
AU - Cheff, Dorian M.
AU - Lee, Tobie D.
AU - Bougie, Danielle
AU - Cheng, Ken
AU - Coussens, Nathan P.
AU - Dorjsuren, Dorjbal
AU - Eastman, Richard T.
AU - Huang, Ruili
AU - Iannotti, Michael J.
AU - Karavadhi, Surendra
AU - Klumpp-Thomas, Carleen
AU - Roth, Jacob S.
AU - Sakamuru, Srilatha
AU - Sun, Wei
AU - Titus, Steven A.
AU - Yasgar, Adam
AU - Zhang, Ya Qin
AU - Zhao, Jinghua
AU - Andrade, Rodrigo B.
AU - Brown, M. Kevin
AU - Burns, Noah Z.
AU - Cha, Jin K.
AU - Mevers, Emily E.
AU - Clardy, Jon
AU - Clement, Jason A.
AU - Crooks, Peter A.
AU - Cuny, Gregory D.
AU - Ganor, Jake
AU - Moreno, Jesus
AU - Morrill, Lucas A.
AU - Picazo, Elias
AU - Susick, Robert B.
AU - Garg, Neil K.
AU - Goess, Brian C.
AU - Grossman, Robert B.
AU - Hughes, Chambers C.
AU - Johnston, Jeffrey N.
AU - Joullie, Madeleine M.
AU - Kinghorn, A. Douglas
AU - Kingston, David G.I.
AU - Krische, Michael J.
AU - Kwon, Ohyun
AU - Maimone, Thomas J.
AU - Majumdar, Susruta
AU - Maloney, Katherine N.
AU - Mohamed, Enas
AU - Murphy, Brian T.
AU - Nagorny, Pavel
AU - Olson, David E.
AU - Overman, Larry E.
AU - Brown, Lauren E.
AU - Snyder, John K.
AU - Porco, John A.
AU - Rivas, Fatima
AU - Ross, Samir A.
AU - Sarpong, Richmond
AU - Sharma, Indrajeet
AU - Shaw, Jared T.
AU - Xu, Zhengren
AU - Shen, Ben
AU - Shi, Wei
AU - Stephenson, Corey R.J.
AU - Verano, Alyssa L.
AU - Tan, Derek S.
AU - Tang, Yi
AU - Taylor, Richard E.
AU - Thomson, Regan J.
AU - Vosburg, David A.
AU - Wu, Jimmy
AU - Wuest, William M.
AU - Zakarian, Armen
AU - Zhang, Yufeng
AU - Ren, Tianjing
AU - Zuo, Zhong
AU - Inglese, James
AU - Michael, Sam
AU - Simeonov, Anton
AU - Zheng, Wei
AU - Shinn, Paul
AU - Jadhav, Ajit
AU - Boxer, Matthew B.
AU - Hall, Matthew D.
AU - Xia, Menghang
AU - Guha, Rajarshi
AU - Rohde, Jason M.
N1 - Funding Information: 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).
PY - 2018/12/26
Y1 - 2018/12/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85058666398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058666398&partnerID=8YFLogxK
U2 - 10.1021/acscentsci.8b00747
DO - 10.1021/acscentsci.8b00747
M3 - Article
C2 - 30648156
AN - SCOPUS:85058666398
VL - 4
SP - 1727
EP - 1741
JO - ACS Central Science
JF - ACS Central Science
SN - 2374-7943
IS - 12
ER -