Building Diverse Hit-Finding Collections Through Novel Chemistries

At Sygnature Discovery, we have a long history of building novel screening compound collections. As the nature of targets that are being progressed for drug discovery have become increasingly complex and challenging, the nature of the compound libraries we use for hit finding against these targets have also seen significant changes, recognising the need for better control of physicochemical properties, three-dimensional character and rigidity.

During our participation in the European Lead Factory (ELF), our chemists contributed 41k compounds over 5 years (2013-2018), based on 66 novel 3-dimensional scaffolds. Building upon this success, we have since built our own LeadFinder Prism collection (2018-present day), a novel, high fraction sp3 and proprietary screening collection of >60k compounds unique to Sygnature Discovery. In this poster, we highlight some of the chemistry methodology behind a selection of novel and readily accessible structural scaffolds that we have developed through our compound generation pipeline – each is synthetically tractable and has been used by our High Throughput Chemistry (HTC) team to generate significant numbers of novel, lead-like compounds to enrich hit finding activities.