Recent studies have highlighted the role of transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) in melanoma for cancer survival, invasion, and metastasis. High expression of NR4A1 has also been implicated in tumor-infiltrating immune cells including TI-Treg cells and exhausted CD8+ T cells. My research focuses on developing an NR4A1 degrader using a proteolysis targeting chimera (PROTAC) drug design. The PROTAC can bind to NR4A1 and an E3 ligase to ubiquitinate NR4A1 and degrade it via the ubiquitin-proteasome pathway. By targeting NR4A1, we hope to achieve reduced cancer cell survival, while simultaneously improving the host’s immune response to cancer by reducing the suppressive function of TI-Tregs and re-activating the effector function of exhausted CD8+ T cells.