The continued development of computational and synthetic methods has enabled the enumeration or preparation
of a nearly endless universe of chemical structures. Nevertheless, the ability of this chemical universe to deliver small
molecules that can both modulate biological targets and have drug-like physicochemical properties continues to be a topic
of interest to the pharmaceutical industry and academic researchers alike. The chemical space described by public, commercial,
in-house and virtual compound collections has been interrogated by multiple approaches including biochemical,
cellular and virtual screening, diversity analysis, and in-silico profiling. However, current drugs and known chemical
probes derived from these efforts are contained within a remarkably small volume of the predicted chemical space. Access
to more diverse classes of chemical scaffolds that maintain the properties relevant for drug discovery is certainly needed
to meet the increasing demands for pharmaceutical innovation. The Lilly Open Innovation Drug Discovery platform
(OIDD) was designed to tackle barriers to innovation through the identification of novel molecules active in relevant disease
biology models. In this article we will discuss several computational approaches towards describing novel, biologically
active, drug-like chemical space and illustrate how the OIDD program may facilitate access to previously untapped
molecules that may aid in the search for innovative pharmaceuticals.
Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285 U.S.A.