Discovery of epigenetic chemical probes is an important area of research with potential to deliver drugs for a multitude of diseases. However, commercially available screening libraries often used in drug discovery campaigns contain molecules that are focused on a narrow range of chemical space primarily driven by ease of synthesis and previously targeted enzyme classes (e.g., kinases) resulting in low hit rates for epigenetic targets. In an effort to overcome these limitations, we have proposed a new strategy for the design of epigenetic focused compound collections that will augment existing libraries and present our efforts towards their realization. To showcase this approach we have employed an alpha-alkylamino radical annulation of maleimides to give a focused compound collection based on the tetrahydroquinoline pharmacophore decorated with privileged isosteres. Cheminformatic analysis showed that our library contained unique chemical matter despite being enriched with known isosteres, demonstrating that new regions of epigenetically relevant chemical space can be accessed using our strategy and may enable the discovery of chemical probes against undrugged epigenetic targets.

Targeting epigenetic chemical space with new chemistry

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.