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CB-1158 Hydrochloride (INCB01158 Hydrochloride)

Catalog No.GC34368

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CB-1158 Hydrochloride (INCB01158 Hydrochloride) Chemical Structure

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5mg
$220.00
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10mg
$386.00
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25mg
$754.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment:

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].

Animal experiment:

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. Gemcitabine 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, gemcitabine modestly reduces tumor growth and spares most tumor-infiltrating immune cells, allowing for the evaluation of combination activity with CB-1158[1].

References:

[1]. Steggerda SM, et al. 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.

Background

CB-1158 Hydrochloride is a potent and orally bioavailable inhibitor of arginase, with IC50s of 86 and 296 nM for recombinant human arginase 1 and 2, respectively.

CB-1158 Hydrochloride is a potent and orally-bioavailable inhibitor of arginase, with IC50s of 86 and 296 nM for recombinant human arginase 1 and 2, respectively. CB-1158 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). CB-1158 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. CB-1158 show no effect on NOS. In addition, CB-1158 is not directly cytotoxic to murine cancer cell lines[1].

CB-1158 (100 mg/kg, p.o., twice per day) increases the number of tumor-infiltrating cytotoxic cells and decreases myeloid cells in mice. CB-1158 in combination with PD-L1 blockade or gemcitabine inhibits tumor growth in mice bearing CT26 cancer cells[1].

[1]. Steggerda SM, et al. 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.

Chemical Properties

Cas No. SDF
Canonical SMILES O=C([C@@H](N)C)N1C[C@H](CCCB(O)O)[C@](N)(C(O)=O)C1.Cl.Cl
Formula C11H24BCl2N3O5 M.Wt 360.04
Solubility Water : ≥ 50 mg/mL (138.87 mM);DMSO : < 1 mg/mL (insoluble or slightly soluble) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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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
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Average Rating: 5 ★★★★★ (Based on Reviews and 11 reference(s) in Google Scholar.)

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