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IDO-IN-7

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Chemical Structure| 1402836-58-1 同义名 : NLG919;GDC-0919 analogue;GDC-0919;(±)-NLG-919;RG 6078;IDO-IN-2;NLG-919 analogue
CAS号 : 1402836-58-1
货号 : A136625
分子式 : C18H22N2O
纯度 : 99%+
分子量 : 282.38
MDL号 : MFCD26142661
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(177.07 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 25 mg/mL(88.53 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：
生物活性
描述 IDO1 (Indoleamine 2,3-dioxygenase-1) is a heme-containing monomeric oxidoreductase, which can catalyze the degradation of the essential amino acid tryptophan to N-formyl-kynurenine, an intermediate metabolized through a series of steps to form NAD+. IDO1 is considered to play an important role in the induction of tumor immune tolerance, which can regulate the immunosuppressive mechanisms responsible for tumor escape from host immune surveillance. NLG919 is potent and selective inhibitor of IDO pathway with Ki value of 7nM and EC50 value of 75nM in a cell-based assays, with 15-20 fold more selectivity to IDO than TDO. Using human pDCsIDO1+ in allogeneic MLR reactions, NLG919 could block IDO-induced T cell suppression and restored robust T cell responses with EC50 value of 90nM, as well as with EC50 of 130nM in study using mouse pDCsIDO1+ from tumor-draining lymph nodes. Oral administration of NLG919 dissolved in the water at 3 mg/mL markedly enhanced the anti-tumor responses of naïve and reduced the tumor growth in mice bearing large established B16F10 tumors. An addition of subcutaneous administration at 1 mg/dose twice a day via injection plus 360 µg/day via an SC osmotic pump could enhance antitumor activity[1].
作用机制 The 4-phenylimidazole structure of NLG919 could inhibit IDO1 enzyme activity in noncompetitive manner and bound the heme iron at the IDO1-active site.[2]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.54mL

0.71mL

0.35mL

17.71mL

3.54mL

1.77mL

35.41mL

7.08mL

3.54mL
参考文献

[1]Prendergast GC, Malachowski WP, et al. Discovery of IDO1 Inhibitors: From Bench to Bedside. Cancer Res. 2017 Dec 15;77(24):6795-6811.

[2]Meng X, Du G, et al. Combinatorial antitumor effects of indoleamine 2,3-dioxygenase inhibitor NLG919 and paclitaxel in a murine B16-F10 melanoma model. Int J Immunopathol Pharmacol. 2017 Sep;30(3):215-226.

[3]Gao J, Deng F, et al. Inhibition of Indoleamine 2,3-Dioxygenase Enhances the Therapeutic Efficacy of Immunogenic Chemotherapeutics in Breast Cancer. J Breast Cancer. 2019 Apr 24;22(2):196-209.

[4]Kumar S, Waldo JP, et al. Discovery of Clinical Candidate (1R,4r)-4-((R)-2-((S)-6-Fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1. J Med Chem. 2019 Jul 25;62(14):6705-6733.