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FINDING CURES TOGETHER<sup>SM</sup>

Resources for Understanding the Proper Use of Chemical Tools in Cancer Research

A chemical probe refers to a chemical tool, generally a small molecule, which has utility in interrogating and advancing the understanding of biological systems. The use of these probes can strongly benefit cancer research. However, it is critical that researchers use probes wisely, meaning that the right probe should be applied in the right setting.

The following is a brief guide for the research community to improve the use, discovery, and development of chemical probes in cancer research. Since these probes can have a direct impact on our understanding of biological systems, we hope that this information will improve the quality and integrity of chemistry in all aspects of cancer research. In addition to providing guidance to researchers themselves, we believe that the information provided here may serve as a useful reference to reviewers of literature to ensure that the highest standards are met when small molecules are used as tools in cancer research. Use the links below for more information. 

Chemical Probe Compendiums

There are a number of resources that describe specific chemical probes and the criteria for their quality as probes. Not only is the activity and selectivity profile of these compounds given, but also negative controls and in vivo activities. A number of these organizations will even provide these probes to researchers. Examples are given below:


 Relevant Publications

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Chemical Probe Profiling Resources 

Researchers often face challenges in determining how a compound's cellular activity is related to a biochemical target. Below is a list of vendors and services to help investigators determine whether a particular compound will exhibit target engagement in cells or is selective against a target of interest. It should be noted that these resources are representative and not intended to be comprehensive of the types of services available to the cancer research community. It should also be stressed that the CICR does not endorse using these over alternative services.

  • DiscoverRx. A commercial company that runs panel screening across large target families, particularly kinases.

  • Eurofins. A commercial vendor that also has large panels of target family assays available, such as kinases or GPCRs.

  • KiNativ. Fee-for-service platform that allows the profiling of all native protein and lipid kinases in cell/tissue lysates.

  • NCI-60 Panel. The National Cancer Institute's screen uses 60 different human tumor cell lines and represents leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney cancers. The service is offered at no cost to submitters, although the requests are reviewed prior to screening.

  • Pelago Bioscience. Cellular thermal shift assay (CETSA) based services, e.g. target engagement potency determinations or target agnostic proteome-wide mass spectrometric CETSA drug profiling.

  • Reaction Biology Corporation. A commercial vendor that has large assay panels available, particularly kinase and epigenetic targets.

Relevant Publications

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Ill-suited Probes and Identifying False Positives

These are online resources that provide filters to flag potential "bad actor" compounds:

  • FAF Drugs. This is a free online filter for screening large compound libraries in silico. The tool is described in detail here (open access).

  • Aggregator Advisor. An aggregator advisor database that may help distinguishing between bona fide and artifactual screening hits. This resource is available online and free-of-charge.

  • Promiscuous compounds and other ill-suited probes within Chemical Probes.org is a link to a set of compounds that is commonly misused and should be avoided if at all possible

Relevant Publications

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Volunteer CICR-AACR Probes Expert Members

The following is a running list of CICR-AACR members who have volunteered to serve as a resource to research in need of discussing aspects of chemical probes. If you have questions regarding the use of probes or any of the above material, please contact any of the individuals below:

Angela N. Koehler, PhD
(transcriptional regulators; protein-protein interactions)
Massachusetts Institute of Technology (MIT)
koehler@mit.edu

Michael R. Michaelides, PhD
(kinases,  protein-protein interaction targets, epigenetic targets (HDACs, HMTs, HATs))
AbbVie Inc.
michael.michaelides@abbvie.com

Vinod F. Patel, PhD
APC Therapeutics
vinodfpatel@apctherapeutic.com

Henry Pauls, PhD
University Health Network, Canada
henry.pauls@cogeco.ca

Joachim Rudolph, PhD
(kinases; GTPases)
Genentech, Inc.
joachimr@gene.com

David E. Uehling, PhD
(kinases;  protein-protein interaction targets)
Ontario Institute for Cancer Research, Canada
daviduehling@gmail.com

Alex G. Waterson, PhD
(kinase inhibitors; protein-protein interaction inhibitors; fragment-based drug discovery; structure-guided drug design)
Vanderbilt University School of Medicine
alex.g.waterson@vanderbilt.edu

Iain Watson, PhD
(protein-protein interactions and the ubiquitin proteosome pathway)
Ontario Institute for Cancer Research, Canada
iain.watson@oicr.on.ca

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