Relevance of the Trillion-Sized Chemical Space “eXplore” as a Source for Drug Discovery

Within the past two decades, virtual combinatorial compound
collections,
so-called chemical spaces, became an important molecule source for
pharmaceutical research all over the world. The emergence of compound
vendor chemical spaces with rapidly growing numbers of molecules raises
questions about their application suitability and the quality of the
content. Here, we examine the composition of the recently published
and, so far, biggest chemical space, “eXplore”, which
comprises approximately 2.8 trillion virtual product molecules. The
utility of eXplore to retrieve interesting chemistry around approved
drugs and common Bemis Murcko scaffolds has been assessed with several
methods (FTrees, SpaceLight, SpaceMACS). Further, the overlap between
several vendor chemical spaces and a physicochemical property distribution
analysis has been performed. Despite the straightforward chemical
reactions underlying its setup, eXplore is demonstrated to provide
relevant and, most importantly, easily accessible molecules for drug
discovery campaigns.