Chemical probes are bioactive compounds with a well characterized mechanism of action, which modulate a biological target (e.g., a cellular protein of interest) with high potency and selectivity. They can be used for extracellular and (in the case of cell permeable probes) intracellular targets and can be applied to biological systems in a defined manner with respect to concentration, time of onset and duration of exposure. They typically act directly on the level of the gene-product (i.e., protein-level). Chemical probes also allow for the interrogation of complex biological processes, where other traditional genetic approaches can be limited (e.g., multifunctional proteins, protein complexes, protein families). Importantly, chemical probes play an important role for target validation in drug discovery. Despite these advantages, high quality chemical probes are only available for a small subset of the human proteome, highlighting the need for concerted efforts to develop more high-quality chemical probes.

EU-OPENSCREEN as the European Research Infrastructure for Chemical Biology and early Drug Discovery

One major bottleneck for cell and molecular biologists to develop a chemical probe for their biological target of interest is the limited access to the required automated compound screening platforms, comprehensive screening compound collections, and expertise across various disciplines such as hit-to-lead optimisation, data analysis and visualisation, and chemoproteomics.

With the aim to mitigate this bottleneck, the European research infrastructure EU-OPENSCREEN was established in 2018 to enable and support molecular and cell biologists to implement their own projects in chemical biology and early drug discovery. Through its circa 30 academic partner institutes in 10 European countries, EU-OPENSCREEN offers complementary expertise and instrumentation for the development of novel chemical probes in collaboration with the broader biology community. EU-OPENSCREEN partner sites jointly use a unique diversity compound collection containing commercial as well as proprietary compounds submitted by chemists from all over Europe. The structural data of the compounds and primary screening data are made available to the scientific community through its open-access European Chemical Biology Database.

How does EU-OPENSCREEN support molecular and cell biologists?

There are several helpful online resources available which assist biologists to select appropriate chemical probes. Examples include the Probes & Drugs portal or the Chemical Probes Portal. However, high-quality chemical probes are only available for a small fraction of human proteins. So, if no suitable chemical probe is available for your protein or interest, you may want to consider identifying your own chemical probe. This is a rewarding project, and studies which describe the development of a novel quality probe are often published in high impact journals and are among the most cited publications on that particular biological target.

Molecular biologists and biochemists, who have a robust and HTS amenable assay and are interested in developing novel potent chemical probes for their biological target of interest, can access EU-OPENSCREEN's automated high-throughput screening platforms on a collaborative basis and screen comprehensive, rationally designed screening collections with >100,000 drug-like compounds. As a distributed network of screening platforms across Europe, EU-OPENSCREEN provides a wide variety of different read-out technologies, including image-based screening. Depending on the assay, the screening campaign is usually performed in a 384 format, but other assay formats are available. After the primary screening, EU-OPENSCREEN's medicinal chemists help the biologist to optimise the identified and validated 'hit' compounds during the hit-to-probe optimisation programme.

Watch this video describing how EU-OPENSCREEN supports biologists to implement their chemical probes discovery programmes:

More information

More information on EU-OPENSCREEN, our partner sites, compound libraries, application procedures, database, training courses and much more is available on the EU-OPENSCREEN website. You can also sign up to receive our regular newsletters or follow us on Twitter and LinkedIn. You can also send us by email if you have any further questions and want to discuss your research project in more detail.

Photo by Bilal O. on Unsplash