A startup emerging from David Liu's lab intends to commercialize a small-molecule enzyme inhibitor discovery platform to generate more potent drugs with higher specificity. (Image credit: Rose Lincoln/Harvard Staff Photographer.)

Off-target drug toxicity is a significant concern for drug developers, as it can lead to side effects and other adverse events. Currently, small molecules targeting enzymatic activity are focused on evolutionarily conserved catalytic sites, often yielding ligands with relatively low specificity. To address this lack of specificity, David Liu's laboratory has developed a small-molecule enzyme inhibitor discovery platform that targets distal binding pockets of enzymes (exo-sites) that are not evolutionarily conserved. Combining this approach with DNA-encoded libraries, Exo Therapeutics, a startup emerging from the Liu Lab, intends to commercialize the platform, generating more potent drugs with higher specificity to the targeted substrate. The team has already identified a series of high-value target opportunities within oncology and is focusing its efforts on validation of reprogramming enzymes using exo-site function-selective inhibitors.