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SX-682 is an orally bioavailable small-molecule allosteric inhibitor of CXCR1 and CXCR2 that blocks tumor MDSC recruitment and enhances T cell activation and antitumor immunity.
SX-682 is an orally bioavailable small-molecule allosteric inhibitor of CXCR1 and CXCR2 that blocks tumor MDSC recruitment and enhances T cell activation and antitumor immunity.
Whole tumor accumulation of CXCL1 in vivo in MOC1 and LLC tumors is significantly greater than oral mucosa and normal lung, respectively, and not diminished with SX-682 treatment. Plasma accumulation of CXCL1 is greater in tumor-bearing mice compared with naive for both models and increases following SX-682 treatment. Treatment of mice bearing MOC1 or LLC tumors with SX-682 beginning 10 or 20 days after tumor initiation does not alter CXCR1 or CXCR2 expression on tumor cells in vivo.[2] Following in vivo SX-682 treatment, tumor PMN-MDSC expression of cell surface TGF-β or superoxide dismutase 1/2 genes, responsible for the generation of H2O2, is not significantly altered.[3]
[1] Xin Lu, et al. Nature. 2017 Mar 30;543(7647):728-732. [2] Lillian Sun, et al. JCI Insight. 2019 Apr 4;4(7):e126853. [3] Sarah Greene, et al. Clin Cancer Res. 2020 Mar 15;26(6):1420-1431.
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