Degrading receptor

The term degrading receptor refers to a functional class of cell-surface receptors leveraged in the field of Extracellular Targeted Protein Degradation (eTPD) to eliminate pathogenic proteins. These receptors, which include the asialoglycoprotein receptor (ASGPR), the cation-independent mannose-6-phosphate receptor (CI-M6PR), and various cytokine receptors like CXCR7, possess the natural ability to internalize ligands and transport them to the lysosome for degradation. Therapeutic modalities such as LYTACs, KineTACs, and EpiTACs utilize bispecific molecules to bridge a target protein of interest (POI) to a degrading receptor, thereby hijacking the receptor's internalizing machinery to clear the POI from the extracellular space or cell surface. This approach is particularly valuable for targeting undruggable proteins, such as secreted factors and membrane-bound receptors involved in cancer, inflammation, and neurodegeneration. By facilitating the catalytic removal of these proteins, degrading receptors offer a potent alternative to traditional occupancy-driven inhibitors.

Other names

Lysosome-targeting receptorInternalizing receptorClearance receptorRecycling receptorEndocytic receptor

Targeted protein degradation (TPD) via the recruitment of a target protein to a degrading receptor, which induces internalization and trafficking to the lysosome for proteolysis.