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Chemical Probes (Classical Modulators) Criteria
Chemical probes (classical modulators) are small-molecule ligands targeting specific biomolecular targets (proteins). They allow scientists to ask mechanistic and phenotypic questions about a target in cell-based or animal studies.
Chemical probes play a major role in linking a phenotype to a gene allowing the functional annotation of the human genome and validating new molecular targets. When a phenotype is observed upon treatment with the chemical probe, it is attributed to the protein targeted by the probe hence selectivity and potency, are essential attributes of chemical probes.
The Chemical Probes Team has put together a list of criteria to be used when selecting a probe for your experiment.
|Activity||Evidence of target binding/activity modulation. (In-vitro IC50/Ki/Kd, etc.)|
|Control Compounds||Similar structure with similar physicochemistry, non-binding against target|
|Off-target activity||Evidence of wider in vitro profiling, especially within protein class|
Evidence and quantification of target engagement
|Off-target activity in cells|
|Evidence of cellular permeability||Demonstrable by steps above|
- Antolin AA, Workman P, Al-Lazikani B. Public resources for chemical probes: the journey so far and the road ahead. Future Med Chem. 2021 Apr;13(8):731-747. doi: 10.4155/fmc-2019-0231.
- Arrowsmith CH, et al. The promise and peril of chemical probes. Nat Chem Biol. 2015; 11, 536-541 doi: 10.1038/nchembio.1867.
- Blagg J, Workman P. Choose and use your chemical probe wisely to explore cancer biology. Cancer Cell. 2017; 32, 9-25 doi: 10.1016/j.ccell.2017.06.005.
- Bunnage ME, Chekler EL, Jones LH. Target validation using chemical probes. Nat Chem Biol. 2013; 9, 195-199 doi: 10.1038/nchembio.1197.
- Frye SV. The art of the chemical probe. Nat Chem Biol. 2010; 6, 159-161 doi: 10.1038/nchembio.296.
- Workman P, Collins I. Probing the probes: fitness factors for small molecule tools. Chem Biol. 2010; 17, 561-577 doi: 10.1016/j.chembiol.2010.05.013.