Physicochemical Properties
| Molecular Formula | C11H24BCL2N3O5 |
| Molecular Weight | 360.04 |
| Appearance | Solid powder |
| Synonyms | CB-1158 dihydrochloride; INCB01158 dihydrochloride |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | IC50: 86 nM (Arginase 1), 296 nM (Arginase 2)[1] |
| ln Vitro | Numidargistat dihydrochloride is a potent and orally bioavailable arginase inhibitor with IC50 of 86 and 296 nM for recombinant human arginase 1 and 2, respectively. Numidargistat dihydrochloride inhibits native arginase 1 (Arg1) in human granulocyte, erythrocyte and hepatocyte lysates with IC50 of 178 nM, 116 nM and 158 nM, respectively, and blocks Arg1 in plasma from cancer patients (IC 50, 122 nM). Numidargistat dihydrochloride also exhibits potent inhibitory activity against arginase in human HepG2, K562 cell lines and primary human hepatocytes with IC50 of 32, 139, 210 μM, respectively. Numidargistat dihydrochloride has no effect on NOS. In addition, Numidargistat dihydrochloride has no direct cytotoxicity against mouse cancer cell lines [1]. |
| ln Vivo | Numidargistat dihydrochloride (100 mg/kg, PO, twice daily) increases the number of tumor-infiltrating cytotoxic cells and decreases bone marrow cells in mice. Numidargistat dihydrochloride combined with PD-L1 blocker or LY 188011 inhibits tumor growth in mice bearing CT26 cancer cells [1]. |
| References |
[1]. Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment. J Immunother Cancer. 2017 Dec 19;5(1):101. [2]. Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment. J Immunother Cancer. 2017 Dec 19;5(1):101. |
Solubility Data
| Solubility (In Vitro) |
DMSO : 55 mg/mL (152.76 mM; with sonication) H2O : 37.78 mg/mL (104.93 mM; with sonication) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 3.25 mg/mL (9.03 mM) in 10% DMSO 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension; sonication. For example, if 1 mL of working solution, add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix. *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (7.64 mM)(Saturation unknown) in 5% DMSO 40% PEG300 5% Tween-80 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: ≥ 1.38 mg/mL (3.83 mM)(Saturation unknown) in 5% DMSO 95% (20% SBE-β-CD in Saline) (these cosolvents were added sequentially from left to right, one at a time), clear solution *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7775 mL | 13.8873 mL | 27.7747 mL | |
| 5 mM | 0.5555 mL | 2.7775 mL | 5.5549 mL | |
| 10 mM | 0.2777 mL | 1.3887 mL | 2.7775 mL |