Antibody targeting of E3 ubiquitin ligases for receptor degradation

Abstract Most current therapies that target plasma membrane receptors function by antagonizing ligand binding or enzymatic activities. However, typical mammalian proteins comprise multiple domains that execute discrete but coordinated activities. Thus, inhibition of one domain often incompletely suppresses the function of a protein. Indeed, targeted protein degradation technologies, including proteolysis-targeting chimeras 1 (PROTACs), have highlighted clinically important advantages of target degradation over inhibition 2 . However, the generation of heterobifunctional compounds binding to two targets with high affinity is complex, particularly when oral bioavailability is required 3 . Here we describe the…

• G
  Genentech