1. Metabolic Enzyme/Protease
  2. Indoleamine 2,3-Dioxygenase (IDO)

Navoximod (Synonyms: NLG-1488)

Cat. No.: HY-18770B Purity: 99.99% ee.: 99.69%
Handling Instructions

Navoximod is a potent IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor with Ki/EC50 of 7 nM/75 nM.

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

Navoximod Chemical Structure

Navoximod Chemical Structure

CAS No. : 1402837-78-8

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 990 In-stock
Estimated Time of Arrival: December 31
5 mg USD 900 In-stock
Estimated Time of Arrival: December 31
10 mg USD 1440 In-stock
Estimated Time of Arrival: December 31
50 mg   Get quote  
100 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Navoximod is a potent IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor with Ki/EC50 of 7 nM/75 nM.

IC50 & Target[1]

IDO

7 nM (Ki)

IDO

75 nM (EC50)

In Vitro

Using IDO-expressing human monocyte-derived dendritic cells (DCs) in allogeneic mixed lymphocyte reaction (MLR) reactions, Navoximod (NLG919) potently blocks IDO-induced T cell suppression and restores robust T cell responses with an ED50=80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, Navoximod abrogates IDO-induced suppression of antigen-specific T cells (OT-I) in vitro, with ED50=120 nM[1]. Navoximod inhibits the IDO activity in a concentration-dependent manner with an EC50 of 0.95 μM. PEG2k-Fmoc-NLG(L) is less active (EC50 of 3.4 μM) in inhibiting IDO compared with free Navoximod while PEG2k-Fmoc-NLG(S) is least active (EC50>10 μM). Coculture of IDO+tumor cells with splenocytes isolated from BALB/c mice leads to significant inhibition of T-cell proliferation. This inhibition is significantly attenuated when the mixed cells are treated with Navoximod. PEG2k-Fmoc-NLG(L) is also active in reversing the inhibitory effect of tumour cells although slightly less potent than Navoximod [3].

In Vivo

VNavoximod (NLG919) is orally bioavailable (F>70%); and has a favorable pharmacokinetic and toxicity profile. In mice, a single oral administration of Navoximod reduces the concentration of plasma and tissue Kyn by ~50%. In vivo, in mice bearing large established B16F10 tumors, administration of Navoximod markedly enhances the anti-tumor responses of naïve, resting pmel-1 cells to vaccination with cognate hgp100 peptide plus CpG-1826 in IFA. In this stringent established-tumor model, Navoximod plus pmel-1/vaccine produce a dramatic collapse of tumor size within 4 days of vaccination (~95% reduction in tumor volume compare to control animals receiving pmel-1/vaccine alone without Navoximod)[1]. When combined with Temozolomide (TMZ)+radiation therapy (RT), both Navoximod and 1-methyl-D-tryptophan (D-1MT, indoximod) enhance survival relative to mice treated with TMZ+RT alone[2].

Solvent & Solubility
In Vitro: 

10 mM in DMSO

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.1609 mL 15.8043 mL 31.6086 mL
5 mM 0.6322 mL 3.1609 mL 6.3217 mL
10 mM 0.3161 mL 1.5804 mL 3.1609 mL
*Please refer to the solubility information to select the appropriate solvent.
References
Cell Assay
[3]

The IDO inhibitory effect of PEG2k-Fmoc-NLG is tested by an in vitro IDO assay. Briefly, HeLa cells are seeded in a 96-well plate at a cell density of 5000 cells per well and allowed to grow overnight. Recombinant human IFN-γ is then added to each well with a final concentration of 50 ng/mL. At the same time, various concentrations of PEG2k-Fmoc-NLG(L), PEG2k-Fmoc-NLG(S) or Navoximod (NLG919) (50 nM-20 μM) are added to the cells. After 48 h of incubation, 150 μL of the supernatants per well is transferred to a new 96-well plate. Seventy-five μL of 30% trichloroacetic acid is added into each well and the mixture is incubated at 50°C for 30 min to hydrolyse N-formylkynurenine to kynurenine. For colorimetric assay, supernatants are transferred to a new 96-well plate, mixed with equal volume of Ehrlich reagent (2% p-dimethylamino-benzaldehyde w/v in glacial acetic acid), and incubated for 10 min at RT. Reaction product is measured at 490 nm by a plate reader[3].

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

Animal Administration
[2]

Mice[2]
Mice are anesthetized with 4% isoflurane, and the surgical plane of anesthesia is maintained with 2% isoflurane in oxygen. Mice are immobilized in a stereotactic frame for tumor implantation. Briefly, the skull is shaved and exposed with a 0.5 cm skin incision. With antiseptic technique, 105 GL261 cells (suspended in 3 μL RPMI-1640) are injected at the following coordinates with respect to the bregma on the right side (antero-posterior, -2 mm; medio-lateral, 2 mm; dorso-ventral, 3 mm). This placement reproducibly yielded tumor growth in a paracortical area of the posterolateral right frontal lobe. Tumor-bearing mice are treated with combinations of oral DL-1MT (2 mg/mL D-1MT mixed with 2 mg/mL L-1MT) in drinking water, D-1MT (4 mg/mL) in drinking water, Navoximod (6 mg/mL) in drinking water, intraperitoneal cyclophosphamide, intraperitoneal temozolomide, and/or total-body radiation (500 cGy from a 137Cs source), as detailed in figure legends. Mice are observed daily, and sacrificed when they became ill or moribund[2].

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

References
Molecular Weight

316.37

Formula

C₁₈H₂₁FN₂O₂

CAS No.

1402837-78-8

SMILES

O[[email protected]](CC1)CC[[email protected]]1([H])[[email protected]](O)C[[email protected]@H]2N3C(C4=C2C(F)=CC=C4)=CN=C3

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Purity: 99.99% ee.: 99.69%

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Cat. No.: HY-18770B