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The promise and peril of chemical probes
Cheryl H Arrowsmith1,2, James E Audia3, Christopher Austin4, Jonathan Baell5, Jonathan Bennett6, Julian Blagg7, Chas Bountra8, Paul E Brennan8,9, Peter J Brown1, Mark E Bunnage10, Carolyn Buser-Doepner11, Robert M Campbell12, Adrian J Carter13, Philip Cohen14, Robert A Copeland15, Ben Cravatt16, Jayme L Dahlin17, Dashyant Dhanak18, Aled M Edwards1*, Stephen V Frye19, Nathanael Gray20, Charles E Grimshaw21, David Hepworth10, Trevor Howe22, Kilian V M Huber23, Jian Jin2426, Stefan Knapp8,9, Joanne D Kotz27, Ryan G Kruger28, Derek Lowe29, Mary M Mader12, Brian Marsden8, Anke Mueller-Fahrnow30, Susanne Mller8,9, Ronan C OHagan31, John P Overington32,33, Dafydd R Owen10, Saul H Rosenberg34, Brian Roth35, Ruth Ross36, Matthieu Schapira1,36, Stuart L Schreiber27, Brian Shoichet37, Michael Sundstrm38,39, Giulio Superti-Furga23,40, Jack Taunton41,42, Leticia Toledo-Sherman43, Chris Walpole44, Michael A Walters45, Timothy M Willson35,46, Paul Workman7, Robert N Young47 & William J Zuercher35,46
Chemical probes are powerful reagents with increasing impacts on biomedical research. However, probes of poor quality or that are used incorrectly generate misleading results. To help address these shortcomings, we will create a community-driven wiki resource to improve quality and convey current best practice.
npg 201 5 Nature America, Inc. All rights reserved.
About a decade ago, academia substantially increased its eorts in chemical biology and drug
discovery. These eorts arose in part because of the availability of large numbers of uncharacterized potential drug targets emerging from genome sequencing eorts, from the development and commoditization of new screening technologies andfrom the possibility of inventing new medicines. Some of these eorts, perhapsin appreciation of the complexity and capriciousness of drug discovery, set out a more measured objective: to generate small-molecule tools (chemical probes) to help elucidate the roles of the targeted proteins in healthy and diseased cells and tissues.
Over the past decade, we have learned some important lessons from these forays into chemical biology. First, chemical biology has had a major impact on our understanding of human biology andthe treatment of human disease. New chemical biology technologies, such as the cellular thermal shi assay for assessing direct target engagement in cells1 and click chemistry as a means for bioorthogonal functionalization2, are increasingly used in the broader scientic community. High-quality chemical probes have served both
as powerful research tools and as seeds to spur...