UW-Madison researchers have developed a protein degrader that shuttles targeted extracellular protein into the lysosome using a cyclic peptide that binds to a cellular receptor attached to a binding molecule for a protein of interest. Once inside the lysosome, the target protein is released from the molecule and degraded. The shuttling molecule is released back outside of the cell where it can bind another target protein. The researchers tested this bifunctional molecule using a fluorescent label to ensure it entered and exited the lysosome. They labeled an antibody for the cancer target EGFR with the cyclic peptide and measured the presence of EGFR in HepG2, MCF7 and HeLa cells and noted a significant decreased in EGFR protein levels in cells dosed with the cyclic peptide labeled antibody suggesting that EGFR has been degraded in each of the three cell lines.