Navigating large chemical spaces in early-phase drug discovery.

ABSTRACT

The size of actionable chemical spaces is surging, owing to a variety of novel techniques, both computational and experimental. As a consequence, novel molecular matter is now at our fingertips that cannot and should not be neglected in early-phase drug discovery. Huge, combinatorial, make-on-demand chemical spaces with high probability of synthetic success rise exponentially in content, generative machine learning models go hand in hand with synthesis prediction, and DNA-encoded libraries offer new ways of hit structure discovery. These technologies enable to search for new chemical matter in a much broader and deeper manner with less effort and fewer financial resources. These transformational developments require new cheminformatics approaches to make huge chemical spaces searchable and analyzable with low resources, and with as little energy consumption as possible. Substantial progress has been made in the past years with respect to computation as well as organic synthesis. First examples of bioactive compounds resulting from the successful use of these novel technologies demonstrate their power to contribute to tomorrow's drug discovery programs. This article gives a compact overview of the state-of-the-art.