Joint European Compound Library: a unique and diverse collection of compounds
The Joint European Compound Library (JECL) forms the core of the EU Lead Factory. It contains a diverse range of high quality compounds that are synthetically tractable and that can make excellent starting points for drug discovery projects. These compounds come from the proprietary collections of the seven established pharmaceutical (EFPIA) partners of the European Lead Factory and from the project’s own synthetic chemistry programme, and are in general not commercially available. The European Lead Factory provides a unique framework that enables availability of these compound collections to the wider scientific community.
The JECL was initially established with over 300,000 compounds contributed by the seven EFPIA partners from their own libraries, and this set is referred to as the EFPIA collection. A detailed analysis (Besnard et al, 2015, DDT) revealed that this collection has an attractive physicochemical profile (average MW of 350 Da and log P of 2-3) and that the compounds are predicted to show activity in a diverse array of biological targets. The benefit of bringing subsets from multiple companies into a single collection was also apparent with each company’s subset exploring a distinct area of chemical space while local similarity within each subset allows initial Structure Activity Relationships to be investigated.
A key project goal of the EU Lead Factory is to add another 200,000 innovative compounds through its own synthetic chemistry programme. These compounds are carefully selected for novelty, drug-like properties, diversity and synthetic tractability (click here to see the detailed criteria). Library design ideas are crowd sourced from academic and industry chemists across Europe and the compounds are synthesised by the Public Chemistry Consortium. By January 2016, about 80,000 newly synthesized compounds have been added. A recent analysis of the first 50,000 compounds proves that they are extending into chemical space not previously accessible (Karawaczyk et al, 2015, DTT). Compared to other libraries that are available commercially or though similar initiatives, these novel compounds are distinguished by a higher 3D character (fraction sp3 >0.4 for 86% of their library cores) and structurally distinct scaffolds (Tanimoto coefficient <0.2 for intercollection similarity). Together, the EFPIA and Public collections make up the JECL, with currently 400,000 potentially lead-like compounds available for screening.
Drug targets selected by the EU Lead Factory are screened against all compounds in the JECL that are available. Note that the JECL is accessible to the screening centres within the consortium without requiring the disclosure of a compound’s structure. This approach guarantees confidentiality, while it allows a wide range of commercially sensitive compounds to be screened against potential drug targets.
Expansion of chemical space for collaborative lead generation and drug discovery – the European Lead Factory Perspective
A. Karawajczyk, F. Giordanetto, J. Benningshof, D. Hamza, T. Kalliokoski, K. Pouwer, R. Morgentin, A. Nelson, G. Müller, A. Piechot, D. Tzalis
Drug Discov Today. 2015 Nov:20(11):1310-6
doi: 10.1016/j.drudis.2015.09.009 Epub 2015 Sep 30
The Joint European Compound Library: boosting precompetitive research.
Besnard J, Jones PS, Hopkins AL, Pannifer AD.
Drug Discov Today. 2015 Feb;20(2):181-6.
doi: 10.1016/j.drudis.2014.08.014. Epub 2014 Sep 6.
Increasing the delivery of next generation therapeutics from high throughput screening libraries
Wigglesworth M., Murray D.C., Blackett C.J., Kossenjans M. , Nissink J.
Current Opinion in Chemical Biology. 2015, Vol 26.
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