[2-[[5-[(4-fluorophenyl)carbamoyl]pyrimidin-2-yl]sulfanylmethyl]-4-(trifluoromethoxy)phenyl]boronic acid

Description

SX-682 is a novel CXCR1/2 inhibitor (IC50s: CXCR1 = 42 nM, CXCR2 = 20 nM).1?It displayed robust synergistic activity with immune checkpoint blockade against castration resistant prostate cancer.2 It significantly reduced tumor burden in a Ptenfl/fl/Lkb1fl/fl mouse model of lung squamous cell cancer when used in combination with anti-PD1 therapy.3 SX-682 significantly inhibited trafficking of neutrophilic myeloid-derived suppressor cells (PMN-MDSCs) enhancing anti-PD1 immune checkpoint blockade, T cell-based immunotherapy, and NK-cell immunotherapy.4,5

References

Zebala et al. (2015), WO2015/016938 Lu et al. (2017), Effective combinatorial immunotherapy for castration-resistant prostate cancer; Nature 542 728 Kargl et al. (2019), Neutrophil content predicts lymphocyte depletion and anti-PD1 treatment failure in NSCLC; JCI Insight 4 e130850 Sun et al. (2019), Inhibiting myeloid-derived suppressor cell trafficking enhances T cell immunotherapy; JCI Insight 4 e126853 Greene et al. (2020), Inhibition of MDSC Trafficking with SX-682, a CXCR1/2 Inhibitor, Enhances NK-Cell Immunotherapy in Head and Neck Cancer Models; Clin. Cancer Res. 26 1420