A key tool in the earlier stages of drug development is a technique called High Throughput Screening (HTS), in which researchers screen large collections of chemical compounds in the hunt for molecules that could be potential drugs or be used in drug development in other ways. Although pharmaceutical companies have built up large libraries of compounds over the years, access to these collections has been tightly restricted to in-house use by the owners.
Meanwhile, the academic community is becoming increasingly interested in HTS, but public compound collections tend to be rather small and expertise in the area is scattered across many institutions. As a result, few public drug targets have been screened against large, high-quality compound libraries. This has hampered efforts to generate promising leads for the development of innovative drugs.
A unique resource
Enter the European Lead Factory, which provides any researcher in European universities, SMEs and patient organisations with the opportunity to access an industry-like platform for the identification of ‘hits’. Hits are compounds that could potentially be developed into new medicines.
The Joint European Compound Library (JECL) forms the core of the European Lead Factory. The pharmaceutical companies in the consortium have contributed a total of over 300 000 compounds to the project from their proprietary collections. In addition, up to 200 000 novel compounds are being added to the JECL from the project’s own synthetic chemistry programme, the Public Compound Collection (PCC). Chemical library design proposals are sourced from both the European Lead Factory consortium members and from external academics/SMEs. Proposals are selected based on criteria such as novelty, diversity potential, innovative design and synthetic tractability. Once approved, the project’s SMEs, together with the academic institutions, seamlessly translate the most compelling ideas into high quality compound libraries to be shipped to the consortium’s HTS facilities. The JECL forms a unique set of tractable compounds that are not commercially available. They are designed to provide versatile starting points and ample opportunities for further chemical exploration and growth during the hit-to-lead phase.
The European Screening Centre executes the HTS services for the selected public projects from academia and SMEs. It also handles all logistics for the Joint European Compound Collection, acting as a neutral, ‘honest’ broker in the transfer, handling and analysis of confidential data.
Anybody, any target, any disease
The European Lead Factory is open to drug target programmes related to all human disease areas and all types of defined molecular targets. Any researcher from European academia or an SME can access the Joint European Compound Library for screening through the European Screening Centre by submitting their proposal.
Public programmes selected by the project are further advanced by the European Lead Factory. Experts from the project provide guidance in the design of the experiments, support on medicinal chemistry, and help setting up partnerships with others if needed. Once the HTS has been run, the ‘target owner’ (i.e. the organisation that submitted the target for inclusion in the project) will receive a list of a maximum of 50 compounds that have been identified. The large pharmaceutical companies that are partners in the project also have access to the project’s facilities for a defined number of targets under the same conditions.
Strength in diversity
The European Lead Factory unites bright ideas, talent and experience. It combines the power of the pharmaceutical industry’s previously inaccessible compound libraries with the innovation of the academic communities in designing novel compounds and the expertise of many SMEs in HTS and library generation. Importantly, it provides a screening platform of industrial quality focused on value generation. Looking to the future, the European Lead Factory is fast becoming a centre of excellence in Europe for small molecule drug discovery programmes in the public sector. A key output of the project is a comprehensive business plan that will ensure the viability of the initiative once the initial IMI project has ended.