2. Immunology/Inflammation Metabolic Enzyme/Protease
  3. Arginase
  4. Numidargistat dihydrochloride

Numidargistat dihydrochloride  (Synonyms: CB-1158 dihydrochloride; INCB01158 dihydrochloride)

Cat. No.: HY-101979A Purity: 98.65%
COA Handling Instructions

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CB-1158 dihydrochloride (INCB01158 dihydrochloride) est un inhibiteur de arginase qui est puissant et oralement actif, avec des IC50 de 86 nM et 296 nM pour arginase humaine recombinante 1 et arginase humaine recombinante 2, respectivement. Agent d'immuno-oncologie.

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.

For research use only. We do not sell to patients.

Numidargistat dihydrochloride Chemical Structure

Numidargistat dihydrochloride Chemical Structure

Size Price Stock Quantity
Free Sample (0.1 - 0.5 mg)   Apply Now  
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 275 In-stock
Solution
10 mM * 1 mL in DMSO USD 275 In-stock
Solid
5 mg USD 250 In-stock
10 mg USD 450 In-stock
25 mg USD 950 In-stock
50 mg USD 1650 In-stock
100 mg USD 2650 In-stock
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Customer Review

Based on 6 publication(s) in Google Scholar

Other Forms of Numidargistat dihydrochloride:

Numidargistat dihydrochloride Related Antibodies

Top Publications Citing Use of Products

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Numidargistat dihydrochloride Related Antibodies
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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Molecular Weight

360.04

Formula

C11H24BCl2N3O5
Appearance

Solid

Color

White to yellow

SMILES

O=C([C@@H](N)C)N1C[C@H](CCCB(O)O)[C@](N)(C(O)=O)C1.Cl.Cl
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

-20°C, stored under nitrogen, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)

Solvent & Solubility
In Vitro: 

DMSO : 55 mg/mL (152.76 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H2O : 37.78 mg/mL (104.93 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: 3.25 mg/mL (9.03 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 3.25 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (32.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
  • Protocol 2

    Add each solvent one by one:  5% DMSO    40% PEG300    5% Tween-80    50% Saline

    Solubility: ≥ 2.75 mg/mL (7.64 mM); Clear solution

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  PBS

    Solubility: 100 mg/mL (277.75 mM); Clear solution; Need ultrasonic

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).
Purity & Documentation

Purity: 98.65%

COA (254 KB) HNMR (394 KB) RP-HPLC (269 KB) LCMS (100 KB)

Handling Instructions (2659 KB)
References
Cell Assay
[1]

Intracellular arginase activity is determined for the arginase-expressing HepG2 and K-562 cell lines as follows. HepG2 cells are seeded at 100,000 cells per well one day prior to treatment with CB-1158. K-562 cells are seeded at 200,000 cells per well on the day of CB-1158 treatment. Cells are treated with a dose-titration of CB-1158 in SILAC RPMI-1640 media containing 5% heat-inactivated and dialyzed FBS, antibiotics/anti-mycotic, 10 mM L-arginine, 0.27 mM L-lysine, and 2 mM L-glutamine. The medium is harvested after 24 h and urea generated is determined. Wells containing media without cells are used as background controls. For assessing the effect of CB-1158 on Arg1 in primary hepatocytes, frozen human hepatocytes are thawed, allowed to adhere onto collagen-coated wells for 4 h, and then incubated for 48 h in SILAC-RPMI containing 10 mM L-ornithine, no L-arginine, and a dose-titration of CB-1158, at which time the media are analyzed for urea[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
For the 4T1 tumor model, 105 cells are injected orthotopically into the mammary fat pad; for all other tumor models, 106 cells are injected subcutaneously (s.c.) in the right flank. For all studies, CB-1158 is administered by oral gavage twice per day at 100 mg/kg starting on study day 1 (1 day after tumor implant). Control groups receive vehicle (water) twice daily by gavage. Tumor volume measured by digital caliper (length × width × width/2) and body weight are recorded three times per week. Mice are euthanized when tumors necrotize or volumes reach 2000 mm3. For the CT26 model, anti-PD-L1 antibody (5 mg/kg) is injected intraperitoneally (i.p.) on days 5, 7, 9, 11, 13, and 15. For the 4T1 model, anti-CTLA-4 antibody (5 mg/kg) is injected i.p. on days 2, 5, and 8; anti-PD-1 antibody (5 mg/kg) is injected i.p. on days 3, 6, and 9. 4T1 tumors are harvested on study day 25 into Fekete’s solution and tumor nodules are enumerated visually. LY 188011 is dosed 50 mg/kg i.p. on days 10 and 16 for the CT26 model, 60 mg/kg i.p. on days 6 and 10 for the LLC model, or 30 mg/kg i.p. on day 5 for the 4T1 model. With these regimens, LY 188011 modestly reduces tumor growth and spares most tumor-infiltrating immune cells, allowing for the evaluation of combination activity with CB-1158[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
H2O / DMSO 1 mM 2.7775 mL 13.8873 mL 27.7747 mL 69.4367 mL
5 mM 0.5555 mL 2.7775 mL 5.5549 mL 13.8873 mL
10 mM 0.2777 mL 1.3887 mL 2.7775 mL 6.9437 mL
15 mM 0.1852 mL 0.9258 mL 1.8516 mL 4.6291 mL
20 mM 0.1389 mL 0.6944 mL 1.3887 mL 3.4718 mL
25 mM 0.1111 mL 0.5555 mL 1.1110 mL 2.7775 mL
30 mM 0.0926 mL 0.4629 mL 0.9258 mL 2.3146 mL
40 mM 0.0694 mL 0.3472 mL 0.6944 mL 1.7359 mL
50 mM 0.0555 mL 0.2777 mL 0.5555 mL 1.3887 mL
60 mM 0.0463 mL 0.2315 mL 0.4629 mL 1.1573 mL
80 mM 0.0347 mL 0.1736 mL 0.3472 mL 0.8680 mL
100 mM 0.0278 mL 0.1389 mL 0.2777 mL 0.6944 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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Numidargistat dihydrochloride Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

NumidargistatCB-1158INCB01158CB1158CB 1158INCB 01158INCB-01158ArginaseInhibitorinhibitorinhibit

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