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    NLG919
    NLG919

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0939
    CAS #: 1402836-58-1Purity ≥98%

    Description: NLG919 analog (also known as RG6078 analog; GDC0919 analog; IDO-IN-7; NLG-919 analogue; GDC-0919 analogue) is a novel, potent and orally bioavailable inhibitor of IDO (indoleamine-(2,3)-dioxygenase) pathway with Ki/EC50 of 7 nM/75 nM in cell-free assays.  It has potential immunomodulating and antineoplastic activities. NLG919 targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the essential amino acid tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, this agent increases tryptophan levels, restores the proliferation and activation of various immune cells, including NK cells, T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells.

    References: J Immunother Cancer. 2014 Jul 7;2:21; AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 491.

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    Molecular Weight (MW)282.38
    FormulaC18H22N2O
    CAS No.1402836-58-1
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 15 mg/mL warmed (53.1 mM)
    Water: <1 mg/mL
    Ethanol: 30 mg/mL (106.2 mM)
    SMILES CodeOC(C1CCCCC1)CC(C2=C3C=CC=C2)N4C3=CN=C4
    SynonymsIDO-IN 7; IDO IN-7; IDO IN 7; RG6078 analog; GDC-0919; GDC0919 analog; GDC 0919; NLG919; NLG 919 analog; NLG-919; RG-6078; RG 6078.


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    In Vitro

    In vitro activity: 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.


    Kinase Assay: IDO-IN-7 (NLG-919 analogue) is a a potent IDO1 inhibitor with an IC50 of 38 nM.


    Cell Assay: NLG919 potently blockes IDO-induced T cell suppression and restores robust T cell responses with an EC50=90 nM. NLG919 also abrogates IDO-induced suppression of antigen-specific T cells (OT-I or pmel-1) in vitro, (ED50=130 nM ) using mouse IDO+ pDCs from tumor-draining lymph nodes.

    In VivoIn 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.
    Animal modelMice bearing large established B16F10 tumor 
    Formulation & DosageDissolved in water at 3 mg/mL; 6 mg/day injected via IP, or administered subcutaneously at 1 mg/dose twice a day via injection plus 360 μg/day via an SC osmotic pump.
    ReferencesJ Immunother Cancer. 2014 Jul 7;2:21; AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 491.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    NLG919
    IDO-blockade synergizes with chemo-radiation therapy. J Immunother Cancer. 2014 Jul 7;2:21. 
     

    NLG919

    Inhibition or absence of IDO triggers widespread complement deposition in tumors after chemo-radiation therapy. J Immunother Cancer. 2014 Jul 7;2:21. 
     

    NLG919

    Complement is mechanistically required for IDO-blockade to synergize with chemo-radiation therapy. J Immunother Cancer.2014 Jul 7;2:21. 
     

    NLG919

    Bone marrow-derived leukocytes aggregate around tumor blood vessels after chemotherapy treatment alone. J Immunother Cancer. 2014 Jul 7;2:21. 
     

    NLG919

    IDO-blockade drives vascular activation after chemotherapy and tumor necrosis after chemo-radiation therapy. J Immunother Cancer. 2014 Jul 7;2:21. 
     

    NLG919

    Proposed sequence of events. J Immunother Cancer. 2014 Jul 7;2:21. 


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