The advent of “PROTAC®” molecules, heterobifunctional molecules that recruit E3 ligase for targeted protein degradation has added a new dimension to proteostasis-based therapy. Although PROTACs have several advantages over simple inhibitors their development as drugs remains a challenging endeavor due to their unfavorable physicochemical properties. Molecular Glues (MGs) on the other hand are much smaller, drug-like molecules that can promote E3 ligase mediated degradation of therapeutic targets. Progenra has developed several molecular glue degraders against multiple target proteins. We are rapidly expanding the molecular glue degrader chemical space by employing our innovative UbiProTM discovery platform.
Molecular Glue Mechanism of Action-
The schematic describes the action of a Molecular Glue molecule (MG) that binds to an E3 ligase and induces E3 interaction with a specific target protein (T). The E3 ligase then attaches ubiquitin (U) to the target protein. The highly efficient E3 ligase builds a chain of poly-ubiquitin on the target protein which is recognized by the proteasome and the target protein is degraded. The key feature of Molecular Glue is the efficiency with which single molecule is recycled to capture and degrade target proteins.