Fig. 4
From: Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy
Small-molecule degraders hijacking the inherent UPS. PROTACs, molecular glues and hydrophobic tags all hijack intracellular E3 ligases and recruit targeted proteins for ubiquitination and subsequent degradation. Both PROTACs and hydrophobic tags are heterobifunctional small-molecule degraders containing a ligand of a protein of interest, which can recruit E3 ligase through specific ligand and hydrophobic group, respectively. Molecular glues, a class of proximity-inducing small molecules, can modify the substrate-recognizing site of E3 ligase by direct contact, allowing it interaction with neosubstrates