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Metabolic Enzyme/Protease-
NLG919 ??????????????????IDO(indoleamine-(2???3)-dioxygenase) ????????????Ki/EC50??? 7 nM/75 nM???
Indoleamine 2,3-Dioxygenase (IDO)
相关产品
INCB 024360-Indoximod-IDO5L-Navoximod-β-Lapachone-IDO-IN-4-8-Nitrotryptanthrin-IDO-IN-1-IDO-IN-3-PF-06840003-IDO-IN-2-
生物活性
Description
NLG919 is a potentIDO(indoleamine-(2,3)-dioxygenase) pathway inhibitor withKi/EC50of 7 nM/75 nM.
IC50& Target
EC50: 75 nM (IDO)[1]
Ki: 7 nM (IDO)[1]
In Vitro
Using IDO-expressing human monocyte-derived DCs in allogeneic MLR reactions, NLG919 potently blocks IDO-induced T cell suppression and restored robust T cell responses with an ED50=80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, NLG919 abrogates IDO-induced suppression of antigen-specific T cells (OT-I) in vitro, with ED50=120 nM[1].
In Vivo
NLG919 is orally bioavailable (F>70%); and has a favorable pharmacokinetic and toxicity profile. In mice, a single oral administration of NLG919 reduces the concentration of plasma and tissue Kyn by ~50%. In vivo, in mice bearing large established B16F10 tumors, administration of NLG919 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, NLG919 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 NLG919)[1]. When combined with Temozolomide (TMZ)+radiation therapy (RT), both NLG919 and 1-methyl-D-tryptophan (D-1MT, indoximod) enhance survival relative to mice treated with TMZ+RT alone[2].
References
[1].Mario R. Mautino, et al. Abstract 491: NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy. AACR 104th Annual Meeting 2013; Apr 6-10, 2013.
[2].Li M, et al. The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma. J Immunother Cancer. 2014 Jul 7;2:21.