Numidargistat (CB-1158) is a potent and orally active inhibitor of arginase , with IC 50 s of 86 nM and 296 nM for recombinant human arginase 1 and recombinant human arginase 2 , respectively. Immuno-oncology agent
In Vitro
Numidargistat is a potent and orally-bioavailable inhibitor of arginase, with IC 50 s of 86 and 296 nM for recombinant human arginase 1 and 2, respectively. Numidargistat inhibits native rginase 1 (Arg1) in human granulocyte, erythrocyte, and hepatocyte lysate with IC 50 s of 178 nM, 116 nM and 158 nM, respectively, and blocks Arg1 in cancer patient plasma (IC 50 , 122 nM). Numidargistat also exhibits potent inhibitory activity against arginase in human HepG2, K562 cell lines and primary human hepatocytes with IC 50 s of 32, 139, 210 μM, respectively. Numidargistat show no effect on NOS. In addition, Numidargistat is not directly cytotoxic to murine cancer cell lines. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Numidargistat (100 mg/kg, p.o., twice per day) increases the number of tumor-infiltrating cytotoxic cells and decreases myeloid cells in mice. Numidargistat in combination with PD-L1 blockade or gemcitabine inhibits tumor growth in mice bearing CT26 cancer cells . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
