Probe Evaluation

Drawing from their experience and expertise, SERP members review the data for a given probe as well as the publication reporting the probe, and based on this they 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 system 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 types of 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. However, we do provide guidelines for different types of probes to the SERP members to be considered when evaluating probes. These criteria can be found here. Expert reviewers bring their experience and knowledge of how small molecules interact with protein targets and the 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, views about control compounds such as orthogonal probes and inactive analogues that should be used in tandem with the probe, and thoughts on the recommended concentrations to be used. SERP reviewers may also be aware of other potential pitfalls that users should consider before they begin an experiment and risk mitigation steps that can be taken and can pass this information on. 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 these 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 independent ratings from each SERP reviewer are also shown with each review. If no stars are shown (i.e., for in animal use of some probes), then the probe was not considered for this application. In addition to SERP reviewer comments, the Portal staff may also add comments that are marked as such. 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 correspond to the following levels of recommendation.

• 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.