Discovery of fully synthetic FKBP12-mTOR molecular glues

Molecular glues are a new drug modality with the potential to engage otherwise undruggable targets. However, the rational discovery of molecular glues for desired targets is a major challenge and most known molecular glues have been discovered by serendipity. Here we present the first fully synthetic FKBP12-mTOR molecular glues, which were discovered from a FKBP-focused, target-unbiased ligand library. Our biochemical screening of >1000 in-house FKBP ligands yielded one hit that …