CB-1158 (dihydrochloride)

INCB01158 (dihydrochloride)

C11H24BCl2N3O5

DMSO : < 1 mg/mL (insoluble or slightly soluble); H2O : >= 50 mg/mL (138.87 mM)

Immunology/Inflammation; Metabolic Enzyme/Protease

CB-1158 dihydrochloride (INCB01158 dihydrochloride) is a potent and orally bioavailable inhibitor of arginase, with IC₅₀s of 86 and 296 nM for recombinant human arginase 1 and 2, respectively. IC50 & Target: IC50: 86 nM (Arginase 1), 296 nM (Arginase 2)^[1] In Vitro: CB-1158 dihydrochloride is a potent and orally-bioavailable inhibitor of arginase, with IC₅₀s of 86 and 296 nM for recombinant human arginase 1 and 2, respectively. CB-1158 inhibits native rginase 1 (Arg1) in human granulocyte, erythrocyte, and hepatocyte lysate with IC₅₀s of 178 nM, 116 nM and 158 nM, respectively, and blocks Arg1 in cancer patient plasma (IC₅₀, 122 nM). CB-1158 also exhibits potent inhibitory activity against arginase in human HepG2, K562 cell lines and primary human hepatocytes with IC₅₀s of 32, 139, 210 uM, respectively. CB-1158 shows no effect on NOS. In addition, CB-1158 is not directly cytotoxic to murine cancer cell lines^[1]. In Vivo: CB-1158 (100 mg/kg, p.o., twice per day) increases the number of tumor-infiltrating cytotoxic cells and decreases myeloid cells in mice. CB-1158 in combination with PD-L1 blockade or gemcitabine inhibits tumor growth in mice bearing CT26 cancer cells^[1].