Navoximod

Catalog No.S8957 Batch:S895701

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Technical Data

Formula

C18H21FN2O2

Molecular Weight 316.37 CAS No. 1402837-78-8
Solubility (25°C)* In vitro DMSO 63 mg/mL (199.13 mM)
Ethanol 63 mg/mL (199.13 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Navoximod (GDC-0919, NLG-919) is a potent inhibitor of IDO (indoleamine-(2,3)-dioxygenase) pathway with Ki of 7 nM and EC50 of 75 nM.
Targets
IDO [1]
(Cell-free assay)
IDO [1]
(Cell-free assay)
7 nM(Ki) 75 nM(EC50)
In vitro

NLG919 potently blocks IDO-induced T-cell suppression and restored robust T-cell responses with ED50 of 80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, NLG919 abrogated IDO-induced suppression of antigen-specific T cells (OT-I) in vitro, with ED50 of 120 nM. [1]

NLG919 increases the cytotoxic activity toward B16-F10 cells in the presence of pretreatment with interferon (IFN)-γ in vitro.[3]

In vivo

In mice, a single oral administration of NLG919 reduces the concentration of plasma and tissue Kyn by ~ 50%. In mice bearing B16F10 tumors, NLG919 markedly enhances the antitumor responses of naive, resting pmel-1 cells to vaccination with cognate hgp100 peptide plus CpG-1826 in IFA.[1]

Immune competent mice are injected orthotopically with genetically engineered murine glioma cells and treated with GDC-0919 alone or combined with RT. GDC-0919 demonstrates potent inhibition of this node and effectively crosses the blood brain barrier. Although GDC-0919 as a single agent does not demonstrate anti-tumor activity, it has a strong potential for enhancing RT response in glioblastoma, which is further augmented with a hypofractionated regimen.[2]

Protocol (from reference)

Cell Assay:

[3]

  • Cell lines

    the murine melanoma cell line B16-F10

  • Concentrations

    100 nM

  • Incubation Time

    12 h, 24 h, 48 h, 72 h

  • Method

    B16-F10 cells are diluted to 1 × 105 cells/mL with DMEM supplemented with 10% FBS and seeded at 2 mL per well into 6-well plates. The culture medium is replaced with fresh growth medium with or without 25 ng/mL IFN-γ for 10–12 h after seeding. After incubation with IFN-γ for 24 h, the medium is replaced with fresh medium containing 100 nM NLG919, 3 nM PTX, or a combination of 100 nM NLG919 and 3 nM PTX, and medium containing 0.1% DMSO is used as the vehicle treatment. PTX at 3 nM is a concentration with low inhibition rate (IR) of cell growth about 20%. At 0, 12, 24, 48, and 72 h after addition of drugs, cells are washed to remove dead cells and particles. Adherent cells are trypsinized and counted using a CountStar IC1000 Automated Cell Counter (Ruiyu-Biotech). Viability of the counted cells is confirmed by 0.1% blue exclusion. The effect of NLG919 and PTX on the growth of cells is analyzed by plotting cell growth curves using viable cell numbers against time.

Animal Study:

[2]

  • Animal Models

    C57BL/6 (H-2b, CD45.2) mice

  • Dosages

    200 mg/kg

  • Administration

    Oral gavage

Selleck's Navoximod has been cited by 6 publications

Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy [ Acta Pharm Sin B, 2022, 12(6):2695-2709] PubMed: 35755274
Evaluation of Novel Inhibitors of Tryptophan Dioxygenases for Enzyme and Species Selectivity Using Engineered Tumour Cell Lines Expressing Either Murine or Human IDO1 or TDO2 [ Pharmaceuticals (Basel), 2022, 15(9)1090] PubMed: 36145311
Parallel discovery of selective and dual inhibitors of tryptophan dioxygenases IDO1 and TDO2 with a newly-modified enzymatic assay [ Bioorg Med Chem, 2021, 39:116160] PubMed: 33901770
Self-Delivery Photo-Immune Stimulators for Photodynamic Sensitized Tumor Immunotherapy [ ACS Nano, 2020, 10.1021/acsnano.0c06765] PubMed: 33236625
Discovery of Novel Indoleamine 2,3-Dioxygenase 1 (IDO1) and Histone Deacetylase 1 (HDAC1) Dual Inhibitors Derived from the Natural Product Saprorthoquinone [ Molecules, 2020, 25(19)E4494] PubMed: 33007982
Development of an In Vitro Assay to Assess Pharmacological Compounds and Reversion of Tumor-Derived Immunosuppression of Dendritic Cells [ Immunol Invest, 2020, 1-17] PubMed: 32573300

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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