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ACS Cent Sci. 2018 Dec 26;4(12):1727-1741. doi: 10.1021/acscentsci.8b00747. Epub 2018 Dec 5.

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

Author information

1
National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
2
Department of Chemistry, Harvey Mudd College, 301 Platt Boulevard, Claremont, California 91711, United States.
3
Department of Chemistry, Temple University, 1901 North 13th Street, Philadelphia, Pennsylvania 19122, United States.
4
Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, United States.
5
Department of Chemistry, Stanford University, 333 Campus Drive, Stanford, California 94305, United States.
6
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States.
7
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, United States.
8
Natural Products Discovery Institute, Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, Pennsylvania 18902, United States.
9
University of Arkansas for Medical Sciences, 4301 West Markham Street 522, Little Rock, Arkansas 72205, United States.
10
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 4849 Calhoun Road, Houston, Texas 77204, United States.
11
Diamond Age Corp., 344 East Louisiana Street, McKinney, Texas 75069, United States.
12
Department of Chemistry and Biochemistry, UCLA, 607 Charles E. Young Drive East, Los Angeles, California 90095, United States.
13
Department of Chemistry, Furman University, 3300 Poinsett Highway, Greenville, South Carolina 29613, United States.
14
Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506, United States.
15
Scripps Institution of Oceanography, UCSD, 9500 Gilman Drive, La Jolla, California 92093, United States.
16
Department of Chemistry, Vanderbilt University, 7330 Stevenson Center, Nashville, Tennessee 37235, United States.
17
Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
18
College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210, United States.
19
Department of Chemistry, Virginia Tech, 900 West Campus Drive, Blacksburg, Virginia 24061, United States.
20
Chemistry Department, The University of Texas at Austin, 105 East 24th Street STOP A5300, Austin, Texas 78712, United States.
21
Department of Chemistry, University of California Berkeley, 826 Latimer Hall, Berkeley, California 94720, United States.
22
Department of Molecular Pharmacology and Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States.
23
Center for Clinical Pharmacology, St Louis College of Pharmacy and Washington University School of Medicine, 2 Pharmacy Place, St. Louis, Missouri 63110, United States.
24
Department of Chemistry, Point Loma Nazarene University, 3900 Lomaland Drive, San Diego, California 92106, United States.
25
University of Mississippi School of Pharmacy, 2500 North State Street, Jackson, Mississippi 39216, United States.
26
College of Pharmacy, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 South Ashland Avenue, Chicago, Illinois 60607, United States.
27
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
28
Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, United States.
29
School of Medicine, Department of Biochemistry and Molecular Medicine, University of California, Davis, 2700 Stockton Boulevard, Suite 2102, Sacramento, California 95817, United States.
30
Center for Neuroscience, University of California, Davis, 1544 Newton Court, Davis, California 95618, United States.
31
Department of Chemistry, University of California, Irvine, Irvine, California 92697, United States.
32
Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
33
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, United States.
34
Department of Chemistry, University of California Berkeley, 841-A Latimer Hall, Berkeley, California 94720, United States.
35
Department of Chemistry and Biochemistry, and Institute of Natural Products and Research Technologies, University of Oklahoma, 101 Stephenson Parkway, Norman, Oklahoma 73019, United States.
36
Department of Chemistry, Florida Campus, The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, United States.
37
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States.
38
Pharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States.
39
Chemical Biology Program, Sloan Kettering Institute and Tri-Institutional Research Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States.
40
Department of Chemistry and Biochemistry and the Warren Family Research Center for Drug Discovery and Development, University of Notre Dame, 305 McCourtney Hall, Notre Dame, Indiana 46556, United States.
41
Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.
42
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, United States.
43
Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States.
44
Emory Antibiotic Resistance Center, Emory University School of Medicine, 201 Dowman Drive, Atlanta, Georgia 30322, United States.
45
Santa Barbara Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, United States.
46
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong SAR.

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.

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