SX-682 is an orally available allosteric inhibitor of CXCR1 and CXCR2 that blocks tumor myeloid suppressor cell recruitment and enhances T cell activation and anti-tumor immunity, with the potential to treat castration-resistant prostate cancer.

CXCR1:42 nM, CXCR2:20 nM

SX-682 significantly inhibits PMN-MDSC trafficking without altering CXCR2 ligand expression; combination with SX-682 enhances tumor growth inhibition or established tumor rejection following programmed death axis (PD-axis) immune checkpoint blockade or adoptive cell transfer of engineered T cells; CXCR1/2 are expressed on tumor cells, but SX-682 appears to have little direct antitumor effect on these cancer cells. [1]

METHODS: SX-682 (500 mg/kg, oral, one week) was used to treat tumor suppressor model mice injected subcutaneously with MOC2 cells, and PMN-MDSC accumulation was evaluated by flow cytometry.
RESULTS SX-682 significantly reduced PMN-MDSC trafficking into MOC2 tumors, but SX-682 treatment did not alter the proliferation of tumor PMN-MDSC in tumor-bearing mice. The main mechanism of SX-682 is to inhibit PMN-MDSC trafficking into MOC2 tumors. [2]