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

doi:10.1021/acscentsci.8b00747

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 KaravadhiCarleen 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

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

15 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 language	English (US)
Pages (from-to)	1727-1741
Number of pages	15
Journal	ACS Central Science
Volume	4
Issue number	12
DOIs	https://doi.org/10.1021/acscentsci.8b00747
State	Published - Dec 26 2018

ASJC Scopus subject areas

Chemistry(all)
Chemical Engineering(all)

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10.1021/acscentsci.8b00747

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Kearney, S. E., Zahoránszky-Kohalmi, G., Brimacombe, K. R., Henderson, M. J., Lynch, C., Zhao, T., Wan, K. K., Itkin, Z., Dillon, C., Shen, M., Cheff, D. M., Lee, T. D., Bougie, D., Cheng, K., Coussens, N. P., Dorjsuren, D., Eastman, R. T., Huang, R., Iannotti, M. J., ... Rohde, J. M. (2018). Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space. ACS Central Science, 4(12), 1727-1741. https://doi.org/10.1021/acscentsci.8b00747

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. / Canvass : A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space. In: ACS Central Science. 2018 ; Vol. 4, No. 12. pp. 1727-1741.

@article{f0a84d41cd0a46aaaea0bff25385b08b,

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

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.",

author = "Kearney, {Sara E.} and Gergely Zahor{\'a}nszky-Kohalmi and Brimacombe, {Kyle R.} and Henderson, {Mark J.} and Caitlin Lynch and Tongan Zhao and Wan, {Kanny K.} and Zina Itkin and Christopher Dillon and Min Shen and Cheff, {Dorian M.} and Lee, {Tobie D.} and Danielle Bougie and Ken Cheng and Coussens, {Nathan P.} and Dorjbal Dorjsuren and Eastman, {Richard T.} and Ruili Huang and Iannotti, {Michael J.} and Surendra Karavadhi and Carleen Klumpp-Thomas and Roth, {Jacob S.} and Srilatha Sakamuru and Wei Sun and Titus, {Steven A.} and Adam Yasgar and Zhang, {Ya Qin} and Jinghua Zhao and Andrade, {Rodrigo B.} and Brown, {M. Kevin} and Burns, {Noah Z.} and Cha, {Jin K.} and Mevers, {Emily E.} and Jon Clardy and Clement, {Jason A.} and Crooks, {Peter A.} and Cuny, {Gregory D.} and Jake Ganor and Jesus Moreno and Morrill, {Lucas A.} and Elias Picazo and Susick, {Robert B.} and Garg, {Neil K.} and Goess, {Brian C.} and Grossman, {Robert B.} and Hughes, {Chambers C.} and Johnston, {Jeffrey N.} and Joullie, {Madeleine M.} and Kinghorn, {A. Douglas} and Kingston, {David G.I.} and Krische, {Michael J.} and Ohyun Kwon and Maimone, {Thomas J.} and Susruta Majumdar and Maloney, {Katherine N.} and Enas Mohamed and Murphy, {Brian T.} and Pavel Nagorny and Olson, {David E.} and Overman, {Larry E.} and Brown, {Lauren E.} and Snyder, {John K.} and Porco, {John A.} and Fatima Rivas and Ross, {Samir A.} and Richmond Sarpong and Indrajeet Sharma and Shaw, {Jared T.} and Zhengren Xu and Ben Shen and Wei Shi and Stephenson, {Corey R.J.} and Verano, {Alyssa L.} and Tan, {Derek S.} and Yi Tang and Taylor, {Richard E.} and Thomson, {Regan J.} and Vosburg, {David A.} and Jimmy Wu and Wuest, {William M.} and Armen Zakarian and Yufeng Zhang and Tianjing Ren and Zhong Zuo and James Inglese and Sam Michael and Anton Simeonov and Wei Zheng and Paul Shinn and Ajit Jadhav and Boxer, {Matthew B.} and Hall, {Matthew D.} and Menghang Xia and Rajarshi Guha and Rohde, {Jason M.}",

note = "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 (Ministe{\`r} 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{\textquoteright}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).",

year = "2018",

month = dec,

day = "26",

doi = "10.1021/acscentsci.8b00747",

language = "English (US)",

volume = "4",

pages = "1727--1741",

journal = "ACS Central Science",

issn = "2374-7943",

publisher = "American Chemical Society",

number = "12",

}

Kearney, SE, Zahoránszky-Kohalmi, G, Brimacombe, KR, Henderson, MJ, Lynch, C, Zhao, T, Wan, KK, Itkin, Z, Dillon, C, Shen, M, Cheff, DM, Lee, TD, Bougie, D, Cheng, K, Coussens, NP, Dorjsuren, D, Eastman, RT, Huang, R, Iannotti, MJ, Karavadhi, S, Klumpp-Thomas, C, Roth, JS, Sakamuru, S, Sun, W, Titus, SA, Yasgar, A, Zhang, YQ, Zhao, J, Andrade, RB, Brown, MK, Burns, NZ, Cha, JK, Mevers, EE, Clardy, J, Clement, JA, Crooks, PA, Cuny, GD, Ganor, J, Moreno, J, Morrill, LA, Picazo, E, Susick, RB, Garg, NK, Goess, BC, Grossman, RB, Hughes, CC, Johnston, JN, Joullie, MM, Kinghorn, AD, Kingston, DGI, Krische, MJ, Kwon, O, Maimone, TJ, Majumdar, S, Maloney, KN, Mohamed, E, Murphy, BT, Nagorny, P, Olson, DE, Overman, LE, Brown, LE, Snyder, JK, Porco, JA, Rivas, F, Ross, SA, Sarpong, R, Sharma, I, Shaw, JT, Xu, Z, Shen, B, Shi, W, Stephenson, CRJ, Verano, AL, Tan, DS, Tang, Y, Taylor, RE, Thomson, RJ, Vosburg, DA, Wu, J, Wuest, WM, Zakarian, A, Zhang, Y, Ren, T, Zuo, Z, Inglese, J, Michael, S, Simeonov, A, Zheng, W, Shinn, P, Jadhav, A, Boxer, MB, Hall, MD, Xia, M, Guha, R & Rohde, JM 2018, 'Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space', ACS Central Science, vol. 4, no. 12, pp. 1727-1741. https://doi.org/10.1021/acscentsci.8b00747

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.

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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 -