Biology

Openly available chemical tools may speed up development of needed medicines

What happens when industry and academia join forces for the good of science? They launch an open access website that helps researchers to discover new medical treatments.

Chemical probes are important tools in drug discovery research. Chemical biologists frequently use these small molecules to study or manipulate biological systems such as cells and organisms. Although the pharmaceutical industry has generated many high-quality probes, related data is often missing or misleading. This absence of trustworthy data is an obstacle for researchers deciding on which chemical tools to use in their search for new treatments.

To address this lack in accessible knowledge, a group of pharmaceutical companies, universities, hospitals and research organisations joined forces to make a large number of innovative probes and their associated data available to the research community. With partial funding from the EU through the ULTRA-DD project, the partners have launched a website called ‘Open Science Probes’. The site provides information on a unique collection of probes with their related data and control compounds. It also offers information on how to use the molecules and a way to order them. The chemical tools and target-related knowledge made available are described in an article published on the eLife platform.

Probe selection

The probes published on the website meet certain criteria. They have an in vitro potency of less than 100 nM, more than 30-fold selectivity within the target family, extensive off-targets profiling outside the target family and significant cellular on-target activity of less than 1 μM. Furthermore, a 100-times less-potent control compound is available for each probe, and pan-assay interference compounds are excluded. These probes complement the collection generated by the not-for-profit Structural Genomics Consortium and its collaborators.

To guarantee quality, the probes and control compounds undergo a two-tier review process. The first is an internal review performed by partners not involved in the particular probe’s development. The second is conducted externally by independent scientists.

The probes range from novel best-in-class compounds to probes selected because they’re complete sets with control compounds. While some compounds are already commercially available, most of them have no widely characterised partner control compound. The probes cover proteins from a wide range of families of drug targets, such as G protein-coupled receptor, kinases and proteases. They also cover other protein targets associated with the treatment of cancer, inflammatory diseases and neurodegenerative disorders.

The partners hope that the project will encourage other companies and academics to join them and donate probes that will benefit the research community. “[W]e believe this is an exciting first step in uncovering and delivering high-quality chemical probes to unlock new biology and ultimately new high-quality targets for drug discovery,” they state in the eLife article.

Future plans

The next step is to add extra features, such as chemical substructure searches, to the website. Full assay details will be provided and the reagents used will be listed to aid scientists. The project aims to generate more than 70 000 biological data sets within the next 2 years, creating a rich and easily accessible source of information for researchers.

Through its efforts, ULTRA-DD (Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery) is playing an important role in speeding up the development of medicines in areas where they’re urgently needed. The project’s strong open access policy is opening the way to the discovery of new treatments previously hindered through lack of useful knowledge, resources and tools.

For more information, please see:
ULTRA-DD project website

last modification: 2018-06-15 17:15:01



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