Although calculated probes are in a large majority, we established that their scoring is influenced by methodology and biases in data sources. Consequently, the application of PMIS and PDPS scoring retrieves different numbers of quality-rated probes from the Chemical Probes Portal set (i.e. 6:1 in favour of PDPS). We thus support scoring as a pragmatically useful means of compound prioritisation. By combining established criteria, we developed this further to delineate 548 high-quality chemical probes (HQCP) covering just under 450 targets. As we show above, the Swiss-Prot bioactive chemistry crossreferences indicate a data-supported druggable proteome of 20%. The current "probe proteome" targets would reach only 4% dropping to half of that for the HQCP set.