A crowdsourcing evaluation of the NIH chemical probes

Abstract

Between 2004 and 2008, the US National Institutes of Health Molecular Libraries and Imaging initiative pilot phase funded 10 high-throughput screening centers, resulting in the deposition of 691 assays into PubChem and the nomination of 64 chemical probes. We crowdsourced the Molecular Libraries and Imaging initiative output to 11 experts, who expressed medium or high levels of confidence in 48 of these 64 probes.

Figure 1

Heatmap of the confidence scores, by voting member, sorted by the median value. Red and orange indicate high dubiosity, yellow reflects medium values, whereas shades of blue indicate high confidence scores; grey indicates absence of score. The heatmap is sorted by the median score on the vertical axis, and by the research area of the CSG experts on the horizontal axis. The first two columns reflect pharmacokinetics and toxicology, the last four columns reflect a chemical / HTS perspective, whereas the middle five columns are based on cheminformatics tools and experience.

Figure 2

Measured activity (−log₁₀ of the reported target activity, for the intended target) versus estimated aqueous solubility (computed with ALOGPS^{Error! Bookmark not defined.}) for the 64 chemical probes, colored by their qualitative score (red, “high dubiosity”; yellow, “middle”; and blue, “high confidence”, respectively), and labeled by Screening Center.

Figure 3

Rule-of-five^{Error! Bookmark not defined.} overview by molecular weight (MW), computed octanol/water partition coefficient (ClogP), and polar surface area (PSA) for the 64 chemical probes, colored by their qualitative score (see Fig. 2).