The identification of tractable chemical starting points in the drug discovery process relies on both the screening tools that are employed and the chemical input into those screens. High throughput screening is a well-established and very valuable tool for the identification of chemical starting points. In the past decade, virtual screening by computational means has come to play an increasingly important role. Both structure-based and ligand-based virtual screening modalities, coupled with machine learning algorithms, now allow for the profiling of millions of compounds in short order.
The quality and diversity of the chemical used in the screening, be it a wet-lab screening or computational evaluation, is critical to the success of any screening endeavor. Ideally, newly added compounds to a screening library are druglike and are sufficiently novel to allow for easy entry into proprietary chemical space.
The generation of druglike, novel chemical matter has been a core activity at Symeres for many years, and we have participated in a number of efforts to increase the diversity and quality of small molecules in our partners’ screening collections. One activity that deserves highlighting is our organization’s contribution of approx. 80,000 compounds to the European Lead Factory initiative. This public-private partnership has allowed us to explore novel chemistries and develop strong relationships with both industrial and academic partners.
Through our strategic partnership with Axxam, we are now able to offer that compound collection for screening to organizations that do not have an in-house library, or that are interested in expanding the chemical diversity of their existing compound collection. The library consists of a collection of scaffolds that have been enumerated with varying substituents to cover as much druglike space as possible. To the best of our knowledge, the compounds are not present in other library provider’s collections, and the library design principles allow for the expedient synthesis of additional analogues. In addition, scaffold hopping can also be employed to quickly expand the chemical diversity. Some highlights of the physicochemical characteristics are shown below.