The Chemical Probes Portal is a new online resource for anyone using tool compounds in their research. We can learn a lot from high quality chemical probes that are potent, selective, and cell-permeable inhibitors of protein function. Chemical probes with sufficient selectivity enable target validation by defining the role of that target when used in phenotypic assays and disease models.
- in vitro potency of <100 nM
- >30-fold selectivity versus other subfamilies
- demonstration of on-target effect in cells at < 1 μM
Partially selective tools can still be useful, but require more careful data interpretation. In some cases they should be used only in combination with other selective probes or with genetic tools.
This Is Why It Is Important to Know the Selectivity of Chemical Probes
Although the information on probe selectivity and activity in cell-based assays is critical to accurate experimental conclusions, these details are neither easily nor consistently available. The information may be spread piecemeal among a number of publications, behind firewalls, or not published at all.
In order to address the need for ready access to this information, the Chemical Probes Portal has been established as a community-driven resource to provide recommendations on the best available chemical probes and guidance for their use. Kudos to the Wellcome Trust for their support and to the SGC, Institute of Cancer Research, and Broad Institute for their endorsement. As a community resource, it will be most effective if all of us contribute.
Additional Reading on the Role and Value of Chemical Probes
- The Impact of Chemical Probes in Drug Discovery: A Pharmaceutical Industry Perspective. Cell Chemical Biology, 2016, 23:10.
- The Promise and Peril of Chemical Probes. Nature Chemical Biology, 2015, 11:536.
- Probing the Probes: Fitness Factors for Small Molecule Tools, Chemistry & Biology, 2010, 16:561.
DiscoverX Offers the Broadest Range of Profiling Panels for Validation of Chemical Probes
- For GPCR profiling, check out our GPCRscan® and gpcrMAX GPCR Profling Services.
- The KINOMEscan® Kinase Profiling Service and BROMOscan® Bromodomain Profiling Serviceare active-site directed competition binding services that cover 468 kinases and 61 epigenetic targets.
- For validation in the broadest available panel of human primary cell tissue and disease models, the BioMAP® Diversity PLUS™ Phenotypic Profiling Service provides biological validation and supports identification of mechanism of action as well as unexpected off-target activities for a diverse range of targets and pathways.