Numidargistat dihydrochloride (CB-1158 dihydrochloride) is an orally active and highly effective arginase (ARG1) inhibitor, an immuno-oncology agent that inhibits TGF-β2-induced subcapsular cataract by reducing the proliferation of lens epithelial cells (LEC) and decreasing the expression of fibronectin, α-SMA, collagen 1A1, and vimentin.

Arginase II:296 nM, Arginase I:86 nM

Numidargistat dihydrochloride is a potent inhibitor of arginase, inhibiting recombinant human Arg1 (IC50 = 86 nM) and the related enzyme Arg2 (IC50 = 296 nM).
Numidargistat dihydrochloride shows effective inhibitory activity on intracellular arginase in hepatocellular carcinoma (HCC) cell line HepG2, chronic myeloid leukemia cell line K-562, and primary human hepatocytes with IC50 of 32, 139, and 210 μM, respectively. [1]
In mouse lens culture, Numidargistat dihydrochloride (50 μM) and TGF-β2 (10 ng/ml) for 7 days indicated that ASC development could be inhibited by inhibiting ARG1. [2]

In a mouse cancer model, Numidargistat dihydrochloride is given 100 mg/kg twice daily by oral tube feeding, and results show that Numidargistat dihydrochloride blocks arginase, The tumor growth of CT26, LLC, B16 and 4T1 was significantly inhibited. [1]