Joint European Compound Library >500 000 compounds

12 December 2017

The European Lead Factory set out to assemble a screening collection of half a million compounds. Now, that ambitious goal has been reached. A truly pan-consortium achievement.

Since 2013, a total of 500,095 compounds have been aggregated by ELF in the Joint European Compound Library (JECL). Of these, 326,350 were ‘in-kind’ contribution from the seven pharmaceutical industry project partners, who agreed to share part of their proprietary compound collections and with selected target programmes from European researchers. These compounds were delivered at the start of the project, enabling operations to begin as soon as the first target programmes had been selected. Each partner provided sufficient compound in solution for the anticipated 240 screening operations, in a variety of plate and rack formats. They were processed within the first six months and were ready for shipping out to the eight screening groups in July 2013. These initial pooled collections have over the years been enriched by novel, innovative compounds designed and synthesised by consortium chemistry partners. The sum of these high value compounds in the JECL is considered the ‘crown jewels’ of ELF, witnessed as being the ‘best screening collection in the world.’

Exacting criteria have been applied for selecting both the industry contributions and the compounds to be created. So far, >180,000 novel compounds have been synthesised and the five library production partners Edelris, Mercachem, Sygnature, Syncom and Taros are well under way to deliver another ~20,000 compounds before the end of the project. An often underappreciated part of compound design is the practical implementation. Aspects such as cost of goods, atom economy, length and efficiency of the synthetic route, associated diversification steps and purification of final compounds have to be assessed. To this end, feasibility of selected proposals is determined experimentally by academic and industrial consortium partners in the library validation phase. Subsequently, the reagent scope for each of the intended diversity points on a chemical scaffold is probed. By sampling a subset of available building blocks with different reactivity and physicochemical characteristics, valuable information about the accessible chemical diversity is generated. Modifications to the original design based on diversity and practical considerations, identified in the library validation stage, are incorporated into the final library blueprint. Only compounds meeting JECL quality criteria for purity (LC–MS purity >85%, average 97%) and quantity (>5 μmol, average 15 µmol) are added to JECL.

If the compounds are the blood that makes the juices flow, the compound management partner, BioAscent, is the heart of the operations; plating, formatting, storage and delivery. During the process, the compounds are stored into the -20°C automated store, are then picked and formatted as desired by the screening partners and shipped to the eight screening sites. Once screening is completed, the storage system permits rapid cherry-picking of the most promising hit compounds for follow-up testing and eventual removal of successful compounds which are delivered to the target programme owner. To date, 32,350 screening plates have been produced, a total of 250,624 cherry-picked samples have been requested and 4,704 qualified hits for 112 different targets have been ordered, with an overall average turnaround time of 3,5 working days.