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].
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].
Kinase Assay
Cell Assay
Animal Administration
References
Return Policy
If you are in any way unsatisfied with your purchase, you may return any item(s) within 365 days of its original purchase date.
Please provide your Order Number in the email. We strive to reply to all email inquiries within one business day.
