Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space
| Autor: | Rajarshi Guha, Anton Simeonov, Jesus Moreno, Min Shen, Yi Tang, James Inglese, Jared T. Shaw, Jimmy Ming-Tai Wu, Samir A. Ross, Tobie D. Lee, Surendra Karavadhi, Dorian M. Cheff, Susruta Majumdar, Adam Yasgar, Richard E. Taylor, Sam Michael, Zhengren Xu, Wei Sun, Lucas A. Morrill, David A. Vosburg, Wei Zheng, Corey R. J. Stephenson, Noah Z. Burns, Michael J. Iannotti, Carleen Klumpp-Thomas, Richard T. Eastman, Ohyun Kwon, Armen Zakarian, Yufeng Zhang, Matthew D. Hall, Sara E. Kearney, Ya Qin Zhang, Tongan Zhao, Ken Cheng, Indrajeet Sharma, Nathan P. Coussens, Ruili Huang, Derek S. Tan, Paul Shinn, Michael J. Krische, Caitlin Lynch, Jon Clardy, Larry E. Overman, Kanny K. Wan, Chambers C. Hughes, Madeleine M. Joullié, Thomas J. Maimone, Matthew B. Boxer, Jason A. Clement, A. Douglas Kinghorn, Peter A. Crooks, Brian C. Goess, Robert B. Susick, Gergely Zahoránszky-Kőhalmi, Alyssa L. Verano, Danielle Bougie, Jacob S. Roth, Ben Shen, Dorjbal Dorjsuren, Elias Picazo, Jinghua Zhao, John K. Snyder, Rodrigo B. Andrade, Wei Shi, Jin K. Cha, Brian T. Murphy, Fatima Rivas, William M. Wuest, Jake Ganor, Robert B. Grossman, Pavel Nagorny, Emily Mevers, Enas I. Mohamed, David E. Olson, John A. Porco, Neil K. Garg, Srilatha Sakamuru, Jason M. Rohde, M. Kevin Brown, Menghang Xia, Tianjing Ren, Steve Titus, Christopher Dillon, Mark J. Henderson, Zhong Zuo, Regan J. Thomson, David G. I. Kingston, Lauren E. Brown, Jeffrey N. Johnston, Katherine N. Maloney, Richmond Sarpong, Zina Itkin, Gregory D. Cuny, Ajit Jadhav, Kyle R. Brimacombe |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Natural product General Chemical Engineering General Chemistry Biological potential Space (commercial competition) Data science Chemical library Chemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Workflow chemistry Identification (biology) Cluster analysis QD1-999 Limited resources Research Article |
| Zdroj: | ACS Central Science ACS Central Science, Vol 4, Iss 12, Pp 1727-1741 (2018) |
| ISSN: | 2374-7951 2374-7943 |
| Popis: | 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. Canvass, a crowd-sourced library of natural products, was evaluated through HTS in a spectrum of disease-relevant assays to survey the broad biological potential of natural products in drug discovery. |
| Databáze: | OpenAIRE |
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