Therapeutics Discovery

While human genetics has greatly furthered our understanding of disease states, conventional drug development processes continue to bottleneck the translation of these insights into urgently needed therapeutics. Rapidly translating these basic insights into therapeutics requires methods to quickly validate putative targets in disease to nominate potential liabilities, and uncover new molecules that engage and disrupt target function. To bridge the gap between target nomination and therapeutics development, we are developing a novel approach for molecular glue discovery, an exciting strategy to address key therapeutic targets in human cells. In nature, molecular glues are small molecules that have been refined through natural selection to modulate protein–protein interactions. Inspired by Nature, our lab is uncovering genetically-encodable de novo molecular glues that mediate new protein-protein interactions. We achieve this through genetic code expansion strategies to incorporate privileged protein-binding chemotypes alongside automated in vivo directed evolution methods to refine the structures, binding affinities, and specificities of new molecular glues.