Joint European Compound Library

Joint European Compound Library: a unique and diverse collection of compounds

The Joint European Compound Library (JECL) 2013-2018 was the starting library of the European Lead Factory. It contained a diverse range of high-quality compounds that are synthetically tractable and that can make excellent starting points for drug discovery projects. These compounds came from the proprietary collections of the seven (former) pharmaceutical (EFPIA) partners of the European Lead Factory and from the project’s own synthetic chemistry programme, and were in general not commercially available at that time. The current compound library evolved from the JECL 2013-2018 and is further described here. The European Lead Factory provides a unique framework that enables screening of these compound collections to the wider scientific community.

The JECL 2013-2018 was initially established with over 300,000 compounds contributed by the seven former 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 had an attractive physicochemical profile (average MW of 350 Da and logP of 2-3) and that the compounds were 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 allowed initial structure–activity relationships (SARs) to be investigated.

A key project goal of the EU Lead Factory in the 2013-2018 project was to add another 200,000 innovative compounds through its own synthetic chemistry programme. These compounds were carefully selected for novelty, drug-like properties, diversity and synthetic tractability. Library design ideas were crowdsourced from academic and industry chemists across Europe and the compounds were synthesized by the Public Chemistry Consortium. By May 2018, about 200,000 newly synthesized compounds were added to the JECL. The analysis of the first 50,000 compounds proved that they were extending into chemical space not previously accessible (Karawajczyk et al, 2015, DTT). Compared to other libraries that were available commercially or though similar initiatives, these novel compounds were 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 compounds collections made up the JECL, with around 500,000 lead-like compounds available for screening in the end.