Specifically, PTP1B can dephosphorylate the insulin receptor and its substrates, negatively regulating insulin signaling.579 Consequently, it is considered a potential target for treating diabetes, obesity.580,581 Various PTP1B inhibitors were synthesized, but most of the trials have been terminated due to poor selectivity, insufficient efficiency, and safety concerns.582 Fang et al. designed a PTP1B-targeting PROTAC based on CRBN and PTP1B inhibitors, displaying remarkable degradation activity by 50-fold compared to inhibitor. This evidence concerns the gene PTPN1 and obesity due to melanocortin 4 receptor deficiency.