SP-2-225

SP-2-225 is a selective small molecule inhibitor of histone deacetylase 6 (HDAC6) being developed by Shuttle Pharmaceuticals as a radiation sensitizer and immune modulator. The compound is designed to improve outcomes for cancer patients treated with radiation therapy by modifying the tumor microenvironment (TME). Preclinical research has demonstrated that SP-2-225 can suppress the immunosuppressive M2-like phenotype of tumor-associated macrophages (TAMs) and inhibit their migration toward irradiated tumor cells, potentially by modulating the CCL5-CCR5 axis. In murine models of triple-negative breast cancer and melanoma, the combination of SP-2-225 and radiation therapy resulted in enhanced tumor control, an increased M1/M2 macrophage ratio, and delayed post-irradiation relapse. As of 2023, the drug was undergoing IND-enabling studies to support a planned Phase 1 clinical trial.