Will the chemical probes please stand up?

In 2005, the NIH Molecular Libraries Program (MLP) undertook the identification of tool compounds to expand biological insights, now termed small-molecule chemical probes. This inspired other organisations to initiate similar efforts from 2010 onwards. As a central focus of the Probes & Drugs portal (P&D), we have standardised, integrated and compared sets of declared probe compounds harvested from 12 different sources. This turned out to be challenging and revealed unexpected anomalies. Results in this work address key questions including; a) individual and total structure counts, b) overlaps between sources, c) comparisons with selected PubChem sources and d) investigating the probe coverage of druggable targets. In addition, we developed new high-level scoring schemes to filter collections down to probes of higher quality. This generated 548 high-quality chemical probes (HQCP) covering 447 distinct protein targets. This HQCP collection has been added to the P&D portal and will be regularly updated as established sources expand and new ones release data.

Automated summary

The NIH Molecular Libraries Program started identifying small-molecule chemical probes in 2005, inspiring similar efforts from other organizations since 2010. By standardizing, integrating, and comparing probe compounds from 12 sources, challenges and unexpected anomalies were revealed. A total of 548 high-quality chemical probes covering 447 distinct protein targets were developed and added to the Probes & Drugs portal, with plans for regular updates as new data sources emerge.