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    Indoximod (NLG-8189)
    Indoximod (NLG-8189)

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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 #: V0941
    CAS #: 110117-83-4Purity ≥98%

    Description: Indoximod, also known as NLG8189, and D-1MT (1-Methyl-D-tryptophan), is an IDO pathway inhibitor, it reverses IDO-mediated immune suppression. Indoximod inhibits the enzyme IDO, which degrades the essential amino acid tryptophan, and may increase or maintain tryptophan levels important to T cell function. Tryptophan depletion is associated with immunosuppression involving T cell arrest and anergy.

    References: Cancer Res. 2007 Jan 15;67(2):792-801; Oncoimmunology. 2012 Dec 1;1(9):1460-1468.

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    Molecular Weight (MW)218.25
    FormulaC12H14N2O2
    CAS No.110117-83-4
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 1 mg/mL (4.6 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    SMILES CodeN[[email protected]](CC1=CN(C)C2=CC=CC=C12)C(O)=O
    Synonyms1-Methyl-D-tryptophan; Indoximod; NLG8189; NLG 8189; NLG-8189; D1MT;


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    In Vitro

    In vitro activity: Indoximod significantly reverses the suppression of T cells created by IDO-expressing dendritic cells, using both human monocyte-derived dendritic cells and murine dendritic cells isolated directly from tumor-draining lymph nodes. Indoximod activates a Trp sufficiency signal that stimulates mTOR, and relieves IDO-induced Trp deprivation as well as an autophagic response.


    Kinase Assay: 1MT enantiomers are solubilized in DMSO containing 0.1N HCl and added at concentrations of 100, 50, and 0 µM to wells containing the reaction mixture with tryptophan (0-200 µM) followed by addition of IDO enzyme. Plates are sealed and incubated 1 hr in a humidified 37°C incubator, after which the reactions are terminated by addition of 12.5 µl 30% TCA per well. Plates are then resealed in plastic wrap, incubated 30 min at 50°C to hydrolyze the reaction product N-formylkynurenine to kynurenine, and centrifuged. Supernatants are transferred to a flat-bottom 96-well plate, mixed with 100 µl Ehrlich reagent and incubated 10 min at room temperature. Absorbance at 490 nm is read.


    Cell Assay: The immunosuppressive activity of IDO leads to an increase in the number of T-regulatory cells, as measured by their Foxp3+/CD4+/CD25+ phenotype. Indoximod has also been shown to reduce the number of T-regulatory cells.

    In VivoIn mouse models of transplantable melanoma and transplantable and autochthonous breast cancer, Indoximod (400 mg/kg p.o.) enhances antitumor immunity in the setting of combined chemo-immunotherapy regimens.
    Animal modelMouse B16F10 and 4T1 tumor models
    Formulation & DosageDissolved in  0.5% Tween 80/0.5% Methylcellulose (v/v) in water; 400 mg/kg; p.o. administration
    ReferencesCancer Res. 2007 Jan 15;67(2):792-801; Oncoimmunology. 2012 Dec 1;1(9):1460-1468.


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

    Indoximod (NLG-8189)

    mTOR activity is inhibited by IDO and relieved by either D-1MT (Indoximod (NLG-8189)) or L-1MT. Oncoimmunology. 2012 Dec 1;1(9):1460-1468.
     

    Indoximod (NLG-8189)

    mTOR stimulation by D-1MT relies specifically on Trp depletion and not GCN2. (A) D-1MT specificity. Oncoimmunology. 2012 Dec 1;1(9):1460-1468.
     

    Indoximod (NLG-8189)

    IDO-mediated deprivation of Trp triggers autophagy that is relieved by D-1MT. Oncoimmunology. 2012 Dec 1;1(9):1460-1468.


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