Navoximod

SKU: orb1296225

Description

Navoximod (GDC-0919) is a potent small molecule inhibitor of the indoleamine 2,3-dioxygenase (IDO) pathway, exhibiting a Ki of 7 nM and an EC50 of 75 nM. It has been utilized in both in vitro and in vivo research to investigate immunomodulation, particularly in the fields of oncology and autoimmune disease.

Research Area

Metabolism Research

Key Properties

• CAS Number: 1402837-78-8
• MW: 316.37
• Purity: 99.81% (May vary between batches)
• Formula: C₁₈H₂₁FN₂O₂
• SMILES: [H][C@@]1(CC[C@H](O)CC1)[C@H](O)C[C@H]1c2c(cccc2F)-c2cncn12
• Target: IDO,Indoleamine 2,3-Dioxygenase (IDO)
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (12.64 mM);DMSO:100 mg/mL (316.09 mM)

Bioactivity

• Target IC50:
  IDO:7 nM (Ki)|IDO:75 nM (EC50)
• In Vivo:
  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 na ve, 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 produces a dramatic collapse of tumor size within 4 days of vaccination (~95% reduction in tumor volume compared to control animals receiving pmel-1/vaccine alone without Navoximod) . 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 .
• In Vitro:
  Navoximod potently blocks IDO-induced T cell suppression and restores robust T cell responses (ED50: 80 nM) using IDO-expressing human and mouse dendritic cells (DCs) in allogeneic mixed lymphocyte reaction (MLR) and in vitro models from tumor-draining lymph nodes (ED50: 120 nM) . It inhibits IDO activity in a concentration-dependent manner (EC50: 0.95 μM). PEG2k-Fmoc-NLG(L) is less active (EC50: 3.4 μM) compared to Navoximod, while PEG2k-Fmoc-NLG(S) is the least active (EC50>10 μM). Coculture of IDO+ tumor cells with BALB/c mouse splenocytes shows significant inhibition of T-cell proliferation, which is attenuated by Navoximod. PEG2k-Fmoc-NLG(L) also reverses the inhibitory effect of tumor cells, albeit slightly less potently than Navoximod .
• Cell Research:
  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 the colorimetric assay, supernatants are transferred to a new 96-well plate, mixed with an equal volume of Ehrlich reagent (2% p-dimethylamino-benzaldehyde w/v in glacial acetic acid), and incubated for 10 min at RT. The reaction product is measured at 490 nm by a plate reader .
• Animal Research:
  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 the antiseptic technique, 10^5 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; dorsoventral, 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 .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Indoleamine 2,3-Dioxygenase, Indoleamine 2,3Dioxygenase (IDO), Indoleamine 2,3-Dioxygenase (IDO), Indoleamine2,3Dioxygenase, inhibit, Indoleamine2,3Dioxygenase(IDO), Navoximod, NLG 919, NLG-​919, NLG-?919, NLG919, NLG-919, Inhibitor, GDC 0919, GDC0919, GDC-0919, IDO

Compound Identifiers

PubChem CID

70914230