Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space
Publication in refereed journal


摘要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.
著者Sara E. Kearney, Gergely Zahoránszky-Kőhalmi, 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 Jr., 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
期刊名稱ACS Central Science
出版社American Chemical Society: Open Access Titles / American Chemical Society
頁次1727 - 1741

上次更新時間 2021-18-09 於 23:55