Probe Evaluation

Drawing from their experience and expertise, SERP members review the data for a probe as well as the publication reporting the probe and rate the probe for its in cellular and/or in vivo model systems (e.g., mice). Probes are evaluated for use in these two types of systems independently. This means that a probe can have top marks for cellular use without being suitable for use in model organisms.

While we expect SERP 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. We merely provide guidelines to the SERPs to be considered when evaluating probes. Expert reviewers bring their experience 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, SERP 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 such as orthogonal probes that should be used in tandem with the probe, and are aware of other potential pitfalls before they begin an experiment.

Our SERP 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 appearing on the probe pages represent the average of all ratings provided by SERP 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.