Numidargistat (dihydrochloride)

Numidargistat (CB-1158) dihydrochloride is a potent and orally active inhibitor of arginase, with IC₅₀s of 86 nM and 296 nM for recombinant human arginase 1 and recombinant human arginase 2, respectively. Immuno-oncology agent^[1]. IC50 & Target: IC50: 86 nM (Arginase 1), 296 nM (Arginase 2)^[1] In Vitro: Numidargistat 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. Numidargistat dihydrochloride 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). Numidargistat dihydrochloride also exhibits potent inhibitory activity against arginase in human HepG2, K562 cell lines and primary human hepatocytes with IC₅₀s of 32, 139, 210 μM, respectively. Numidargistat dihydrochloride shows no effect on NOS. In addition, Numidargistat dihydrochloride is not directly cytotoxic to murine cancer cell lines^[1]. In Vivo: Numidargistat dihydrochloride (100 mg/kg, p.o., twice per day) increases the number of tumor-infiltrating cytotoxic cells and decreases myeloid cells in mice. Numidargistat dihydrochloride in combination with PD-L1 blockade or LY 188011 inhibits tumor growth in mice bearing CT26 cancer cells^[1].