CB-1158 is a potent and orally bioavailable inhibitor of arginase (IC50s: 86 and 296 nM for recombinant human arginase 1 and 2).

CB-1158 is not directly cytotoxic to murine cancer cell lines [1]. CB-1158 inhibits native arginase 1 (Arg1) in human granulocyte, erythrocyte, and hepatocyte lysate (IC50s: 178 nM, 116 nM, and 158 nM) and blocks Arg1 in cancer patient plasma (IC50, 122 nM). CB-1158 shows no effect on NOS and it also shows potent inhibitory activity against arginase in human HepG2, K562 cell lines, and primary human hepatocytes (IC50s: 32, 139, 210 μM).

CB-1158 in combination with PD-L1 blockade or gemcitabine inhibits tumor growth in mice bearing CT26 cancer cells. CB-1158 (100 mg/kg, p.o., twice per day) increases the number of tumor-infiltrating cytotoxic cells and decreases myeloid cells in mice.