| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 86 nM (Arginase 1), 296 nM (Arginase 2)[1]
Numidargistat targets arginase 1 (ARG1) and arginase 2 (ARG2). Arginase is an enzyme that hydrolyzes L‑arginine to L‑ornithine and urea. Myeloid‑derived suppressor cells (MDSCs) and tumor‑associated macrophages (TAMs) in the tumor microenvironment express high levels of arginase, which depletes L‑arginine and suppresses T cell proliferation and function. By inhibiting arginase, Numidargistat restores L‑arginine levels in the tumor microenvironment, leading to enhanced T cell activation and anti‑tumor immunity. It is an immuno‑oncology agent designed to reverse arginase‑mediated immune suppression. |
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| 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].
Numidargistat is a potent and orally active inhibitor of arginase, with IC₅0 values of 86 nM and 296 nM for recombinant human arginase 1 and arginase 2, respectively. It is an immuno‑oncology agent. In vitro, Numidargistat dihydrochloride inhibits native arginase 1 in human granulocyte, erythrocyte, and hepatocyte lysates with IC₅0 values of 178 nM, 116 nM, and 158 nM, respectively. It also blocks arginase 1 activity in plasma from cancer patients (IC₅0: 359 nM). By inhibiting arginase, Numidargistat reverses arginine deprivation and restores T cell proliferation and function in the tumor microenvironment. |
| 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].
Numidargistat (100 mg/kg, p.o., twice per day) increases the number of tumor‑infiltrating cytotoxic cells and decreases myeloid cells in mice. In mouse tumor models, oral administration of Numidargistat inhibits arginase activity in the tumor microenvironment, leading to increased numbers of CD8+ T cells and reduced tumor growth. The compound has been evaluated in clinical trials for advanced solid tumors in combination with checkpoint inhibitors (e.g., pembrolizumab). However, no specific tumor growth inhibition data are provided in the search results. |
| Enzyme Assay |
The binding of Numidargistat to arginase 1 and arginase 2 is measured by standard in vitro enzyme activity assays using purified recombinant human arginase 1 or arginase 2. The compound is incubated with the enzyme in the presence of the substrate L‑arginine. The reaction is allowed to proceed, and the amount of urea produced is measured colorimetrically by the alpha‑isonitrosopropiophenone method or by using a coupled enzyme assay. The IC₅0 values (86 nM for ARG1, 296 nM for ARG2) are calculated from dose‑response curves (0.1‑10,000 nM). For cellular assays, human granulocytes, erythrocytes, or hepatocytes are lysed, and arginase activity in the lysates is measured in the presence of Numidargistat at graded concentrations (0.1‑10,000 nM). The IC₅0 values are calculated.
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| Cell Assay |
For cellular assays, human peripheral blood mononuclear cells (PBMCs) or T cells are co‑cultured with arginase‑expressing myeloid cells or with recombinant arginase. Cells are treated with Numidargistat at graded concentrations (0.1‑10,000 nM) for 48‑72 h. T cell proliferation is measured by CFSE dilution or [3H]‑thymidine incorporation. T cell activation is assessed by measuring IFN‑gamma and granzyme B production by ELISA or flow cytometry. For cancer cell line assays, tumor cells are co‑cultured with arginase‑expressing MDSCs, and the effect of Numidargistat on tumor cell viability is assessed by MTT or CellTiter‑Glo assays.
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| Animal Protocol |
For in vivo evaluation of anti‑tumor activity, 6‑8‑week‑old female BALB/c or C57BL/6 mice bearing syngeneic tumors (e.g., CT26 colon carcinoma, MC38 colon carcinoma, or B16‑F10 melanoma) are used. When tumors reach approximately 100‑150 mm3, mice are randomized and treated with Numidargistat dihydrochloride orally by gavage at doses of 100 mg/kg twice daily for 2‑4 weeks. Tumor volumes are measured twice weekly. At the study endpoint, tumors are harvested for flow cytometry analysis of immune cell infiltration (CD8+ T cells, MDSCs, TAMs). Arginase activity in tumor homogenates is measured by colorimetric assay. Plasma arginine levels are measured by LC‑MS. Survival is monitored.
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| ADME/Pharmacokinetics |
Numidargistat dihydrochloride (C₈H1₆BN3O4·2HCl, MW = 291.95 (free base), 364.88 (dihydrochloride), CAS 2095732‑06‑0 (free base)) is a solid powder. For storage, the powder should be kept at -20 degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in water or DMSO (10‑50 mM) can be prepared and stored at -80 degC for up to 6 months or at -20 degC for 1 month. For in vivo oral administration, it can be formulated in 0.5% methylcellulose/0.1% Tween‑80 or in water. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for Numidargistat dihydrochloride are reported. In preclinical studies, it was generally well‑tolerated at doses up to 100 mg/kg twice daily in mice. As a research‑grade compound, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed. No LD₅0 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
- CB-1158 is a potent, selective, and orally-bioavailable small-molecule inhibitor of arginase [1]
- CB-1158 does not readily enter cells, exhibiting IC50 values for intracellular arginase two orders of magnitude higher than for soluble arginases in cell lysates; this may protect hepatic urea cycle Arg1 from inhibition [1] - Hepatic Arg1 is tightly associated in a multi-enzyme complex at the mitochondria with substrate channeling, potentially making it less accessible to CB-1158 compared to cytoplasmic or extracellular arginase [1] - CB-1158 is currently in clinical trials for patients with solid tumor malignancies (NCT02903914) as a monotherapy and in combination with anti-PD-1 [1] - Arg1-expressing myeloid cells are abundant in human tumors across multiple histologies (NSCLC, breast, gastric, colorectal, prostate, pancreatic, ovarian, bladder, renal cell carcinoma, etc.) [1] - Cancer patients have significantly elevated plasma Arg1 and reduced plasma L-arginine compared to healthy volunteers, suggesting immune suppression associated with higher circulating Arg1 [1] Numidargistat (CB‑1158; INCB01158) is an investigational, orally active arginase inhibitor developed by Incyte Corporation as an immuno‑oncology agent. The tumor microenvironment suppresses anti‑tumor immune responses through multiple mechanisms, including the recruitment of immunosuppressive cells such as MDSCs and TAMs that express high levels of arginase, leading to arginine depletion and T cell suppression. By inhibiting arginase, Numidargistat restores arginine levels and enhances T cell function. The compound has been evaluated in Phase 1/2 clinical trials for advanced solid tumors in combination with checkpoint inhibitors (e.g., pembrolizumab). The dihydrochloride salt form is used for improved solubility. The compound is for research use only and has not received full regulatory approval. |
| Molecular Formula |
C11H24BCL2N3O5
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|---|---|
| Molecular Weight |
360.04
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| Appearance |
Solid powder
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| Synonyms |
CB-1158 dihydrochloride; INCB01158 dihydrochloride
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : 55 mg/mL (152.76 mM; with sonication)
H2O : 37.78 mg/mL (104.93 mM; with sonication) |
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| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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