Navoximod (C09-0991-163)

InformationNavoximod 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.TargetsIDO (Cell-free assay); IDO (Cell-free assay) 7 nM(Ki); 75 nM(EC50)In vitroNLG919 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) with ED50 of 120 nM./xa0NLG919 increases the cytotoxic activity of paclitaxel toward B16-F10 cells in the presence of pretreatment with interferon (IFN)-γ in vitro.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.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.Cell Research(from reference)Cell lines：the murine melanoma cell line B16-F10 Concentrations：100/u2009nM Incubation Time：12/u2009h, 24/u2009h, 48/u2009h, 72/u2009h. Specifications and Purity: 10mM in DMSO. Molecular Formula: C18H21FN2O2. Molecular Weight: 316.37. PubChem CID: 70914230. Isomeric SMILES: C1CC(CCC1[C@@H](C[C@H]2C3=C(C=CC=C3F)C4=CN=CN24)O)O.