Drawing from their experience and expertise, SAB members review the data in a probe's submission form as well as the publication reporting the probe and rate the probe for its use in cellular and/or in vivo model systems (e.g., mice). Probes are evaluated for use in these two types of systems independently, meaning that it is not necessary for a probe to be validated for use in model organisms for it to be considered and endorsed by the portal.
While we expect SAB members to consider similar data for each probe (including potency, selectivity, evidence for target engagement, and an understanding of the mechanism by which the probe modulates the target), we have not defined rigid criteria that translate into Portal endorsement. Rather, we enlisted experts so they can bring their experience with and knowledge of how small molecules interact with protein targets and the unique challenges that may come to bear in different situations. In addition to rating probes, SAB members can comment on each probe, providing guidance to users to ensure readers understand the strengths and weaknesses of a probe, know about control compounds that should be used in tandem with the probe, and are aware of other potential pitfalls before they begin an experiment.
Our SAB members provide a star rating (1-4 stars) for each chemical probe they review. Star ratings for each probe are based on the data and whether they are sufficient to demonstrate that the probe is valid for use in cellular systems or in animal models. The star ratings that appear on the probe pages represent the average of all the ratings provided by SAB members, and the number of votes for each probe is indicated. If no stars are shown (i.e., for in animal use of some probes), then the probe was not considered for this application. Please note that not being recommended as a chemical probe for a specific protein target does not mean that a compound may not be useful in other contexts. The star ratings correlate to the following recommendations:
4 stars = Recommended as a probe for this target
3 stars = Best available probe for this target, or a high quality probe that is a useful orthogonal tool
2 stars = Insufficient validation data to recommend
1 star = Not recommended as a probe for this target
The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.