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

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Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space.
ACS Central Science ( IF 12.7 ) Pub Date : 2018-12-05 , DOI: 10.1021/acscentsci.8b00747
Sara E Kearney ₁ , Gergely Zahoránszky-Kőhalmi ₁ , Kyle R Brimacombe ₁ , Mark J Henderson ₁ , Caitlin Lynch ₁ , Tongan Zhao ₁ , Kanny K Wan _{1,

2} , Zina Itkin ₁ , Christopher Dillon ₁ , Min Shen ₁ , Dorian M Cheff ₁ , Tobie D Lee ₁ , Danielle Bougie ₁ , Ken Cheng ₁ , Nathan P Coussens ₁ , Dorjbal Dorjsuren ₁ , Richard T Eastman ₁ , Ruili Huang ₁ , Michael J Iannotti ₁ , Surendra Karavadhi ₁ , Carleen Klumpp-Thomas ₁ , Jacob S Roth ₁ , Srilatha Sakamuru ₁ , Wei Sun ₁ , Steven A Titus ₁ , Adam Yasgar ₁ , Ya-Qin Zhang ₁ , Jinghua Zhao ₁ , Rodrigo B Andrade ₃ , M Kevin Brown ₄ , Noah Z Burns ₅ , Jin K Cha ₆ , Emily E Mevers ₇ , Jon Clardy ₇ , Jason A Clement ₈ , Peter A Crooks ₉ , Gregory D Cuny ₁₀ , Jake Ganor ₁₁ , Jesus Moreno ₁₂ , Lucas A Morrill ₁₂ , Elias Picazo ₁₂ , Robert B Susick ₁₂ , Neil K Garg ₁₂ , Brian C Goess ₁₃ , Robert B Grossman ₁₄ , Chambers C Hughes ₁₅ , Jeffrey N Johnston ₁₆ , Madeleine M Joullie ₁₇ , A Douglas Kinghorn ₁₈ , David G I Kingston ₁₉ , Michael J Krische ₂₀ , Ohyun Kwon ₁₂ , Thomas J Maimone ₂₁ , Susruta Majumdar _{22,

23} , Katherine N Maloney ₂₄ , Enas Mohamed ₂₅ , Brian T Murphy ₂₆ , Pavel Nagorny ₂₇ , David E Olson _{28,

29,

30} , Larry E Overman ₃₁ , Lauren E Brown ₃₂ , John K Snyder ₃₂ , John A Porco ₃₂ , Fatima Rivas ₃₃ , Samir A Ross ₂₅ , Richmond Sarpong ₃₄ , Indrajeet Sharma ₃₅ , Jared T Shaw ₂₈ , Zhengren Xu ₃₆ , Ben Shen ₃₆ , Wei Shi ₃₇ , Corey R J Stephenson ₂₇ , Alyssa L Verano ₃₈ , Derek S Tan _{38,

39} , Yi Tang ₁₂ , Richard E Taylor ₄₀ , Regan J Thomson ₄₁ , David A Vosburg ₂ , Jimmy Wu ₄₂ , William M Wuest _{43,

44} , Armen Zakarian ₄₅ , Yufeng Zhang ₄₆ , Tianjing Ren ₄₆ , Zhong Zuo ₄₆ , James Inglese ₁ , Sam Michael ₁ , Anton Simeonov ₁ , Wei Zheng ₁ , Paul Shinn ₁ , Ajit Jadhav ₁ , Matthew B Boxer ₁ , Matthew D Hall ₁ , Menghang Xia ₁ , Rajarshi Guha ₁ , Jason M Rohde ₁

Affiliation

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

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.

中文翻译：

Canvass：用于探索生物空间的众包天然产物筛选库。

天然产物及其衍生物仍然是新兴治疗潜力的源泉。然而，许多实验室用于生物学评估的资源有限，使得之前分离或合成的化合物大部分或完全未经测试。为了解决这个问题，与学术和行业研究人员合作，组装了 Canvass 天然产物库，用于跨多种基于细胞和生化检测的定量高通量筛选 (qHTS)。该文库在理化性质、结构多样性以及与公开文库中化合物的相似性方面的表征表明，Canvass 文库包含许多与已批准药物相同的结构元素。使用各种质量控制指标对生成的测定数据进行分析，并使用统计方法（例如聚类和复合混杂分析）探索所得的测定概况。然后根据结构类别和活性概况对各个化合物进行分类。本文概述了基于这些分类的差异行为以及值得注意的活动。其中一个亮点是 (-)-2(S)-cathafoline 的活性，它被发现可以稳定内质网中的钙水平。这里描述的工作流程说明了利用自动化和高通量筛选的力量广泛调查天然产物的生物潜力的试点工作。

更新日期：2018-12-05

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