FD03

FD03 is a small molecule degrader targeting Forkhead box protein P3 (FoxP3), the master transcription factor essential for the differentiation, stability, and immunosuppressive function of T regulatory cells (Tregs). Developed by researchers at Northwestern University, FD03 acts as a molecular glue or targeted protein degrader that facilitates the interaction between FoxP3 and its E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1 (STUB1/CHIP). This interaction promotes the ubiquitination and subsequent proteasomal degradation of FoxP3, thereby reducing Treg-mediated immunosuppression. In preclinical studies, FD03 treatment has demonstrated the ability to decrease tumor burden in tumor-bearing mice and shift the intratumoral immune landscape toward an inflammatory, anti-tumor phenotype.