PDL1 degrader-3

PDL1 degrader-3 is a CSN5 degrader that targets human CSN5 with an affinity of 4.53 μM. This compound inhibits the enzymatic activity of CSN5, promoting PD-L1 ubiquitination and subsequent degradation through the ubiquitin-proteasome pathway, thus decreasing PD-L1 expression on tumor cell membranes. PDL1 degrader-3 effectively disrupts the PD-1/PD-L1 interaction, thereby enhancing the tumor immune microenvironment, increasing tumor-infiltrating T-cell immunity, and inhibiting the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). Its antitumor efficacy has been demonstrated in various mouse tumor models, making it a valuable tool for research in colorectal and lung cancer.