PDL1 degrader-3 (comppund e24) is a CSN5-binding antitumor immunomodulator with a human CSN5 Kd of 4.53 μM. PDL1 degrader-3 inhibits CSN5 enzymatic activity, increases PD-L1 ubiquitination, and induces PD-L1 degradation via the ubiquitin-proteasome pathway, reducing PD-L1 expression on tumor cell membranes. PDL1 degrader-3 blocks PD-1/PD-L1 interaction, activates the tumor immune microenvironment, enhances tumor-infiltrating T-cell immunity, and inhibits activation of immunosuppressive MDSCs and Tregs. PDL1 degrader-3 exerts antitumor effects in mouse tumor models. PDL1 degrader-3 can be used for the research of colorectal cancer, lung cancer.
