Home>>Signaling Pathways>> Metabolism>> IDO>>(S)-Indoximod

(S)-Indoximod Sale

(Synonyms: 相思子碱,1-Methyl-L-tryptophan; (S)-NLG-8189) 目录号 : GC60417

An IDO inhibitor

(S)-Indoximod Chemical Structure

Cas No.:21339-55-9

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥495.00
现货
100mg
¥450.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

产品描述

1-methyl-L-Tryptophan is an inhibitor of indoleamine 2,3-dioxygenase (IDO; Ki = 19 ?M).1 It inhibits kynurenine production from primary human monocyte-derived IDO-positive dendritic cells and increases T cell proliferation in an allogeneic mixed lymphocyte reaction (allo-MLR) when used at a concentration of 100 ?M. 1-methyl-L-Tryptophan reverses depressive-like behavior in mice in a Bacillus Calmette-Guerin inflammation-induced model of depression.2 Unlike 1-methyl-D-tryptophan, 1-methyl-L-tryptophan does not have an additive effect on survival induced by cyclophosphamide in an orthotopic murine mammary carcinoma model of 4T1 tumors when administered at a dose of 400 mg/kg twice per day.1

1.Hou, D.-Y., Muller, A.J., Sharma, M.D., et al.Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responsesCancer Res.67(2)792-801(2007) 2.Rana, P., Sharma, A.K., Jain, S., et al.Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in miceJ. Basic Clin. Physiol. Pharmacol.27(6)569-576(2016)

Chemical Properties

Cas No. 21339-55-9 SDF
别名 相思子碱,1-Methyl-L-tryptophan; (S)-NLG-8189
Canonical SMILES N[C@@H](CC1=CN(C)C2=CC=CC=C12)C(O)=O
分子式 C12H14N2O2 分子量 218.25
溶解度 DMSO: 5 mg/mL (22.91 mM; ultrasonic and adjust pH to 5 with HCl) 储存条件 4°C, protect from light
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 4.5819 mL 22.9095 mL 45.819 mL
5 mM 0.9164 mL 4.5819 mL 9.1638 mL
10 mM 0.4582 mL 2.291 mL 4.5819 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置

Research Update

Inhibition of the BTK-IDO-mTOR axis promotes differentiation of monocyte-lineage dendritic cells and enhances anti-tumor T cell immunity

Immunity 2021 Oct 12;54(10):2354-2371.e8.PMID:34614413DOI:10.1016/j.immuni.2021.09.005.

Monocytic-lineage inflammatory Ly6c+CD103+ dendritic cells (DCs) promote antitumor immunity, but these DCs are infrequent in tumors, even upon chemotherapy. Here, we examined how targeting pathways that inhibit the differentiation of inflammatory myeloid cells affect antitumor immunity. Pharmacologic inhibition of Bruton'S tyrosine kinase (BTK) and the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) or deletion of Btk or Ido1 allowed robust differentiation of inflammatory Ly6c+CD103+ DCs during chemotherapy, promoting antitumor T cell responses and inhibiting tumor growth. Immature Ly6c+c-kit+ precursor cells had epigenetic profiles similar to conventional DC precursors; deletion of Btk or Ido1 promoted differentiation of these cells. Mechanistically, a BTK-IDO axis inhibited a tryptophan-sensitive differentiation pathway driven by GATOR2 and mTORC1, and disruption of the GATOR2 in monocyte-lineage precursors prevented differentiation into inflammatory DCs in vivo. IDO-expressing DCs and monocytic cells were present across a range of human tumors. Thus, a BTK-IDO axis represses differentiation of inflammatory DCs during chemotherapy, with implications for targeted therapies.

Indoximod opposes the immunosuppressive effects mediated by IDO and TDO via modulation of AhR function and activation of mTORC1

Oncotarget 2020 Jun 23;11(25):2438-2461.PMID:32637034DOI:10.18632/oncotarget.27646.

Indoximod has shaped our understanding of the biology of IDO1 in the control of immune responses, though its mechanism of action has been poorly understood. Previous studies demonstrated that indoximod creates a tryptophan (Trp) sufficiency signal that reactivates mTOR in the context of low Trp concentrations, thus opposing the effects caused by IDO1. Here we extend the understanding of indoximod'S mechanism of action by showing that it has pleiotropic effects on immune regulation. Indoximod can have a direct effect on T cells, increasing their proliferation as a result of mTOR reactivation. Further, indoximod modulates the differentiation of CD4+ T cells via the aryl hydrocarbon receptor (AhR), which controls transcription of several genes in response to different ligands including kynurenine (Kyn). Indoximod increases the transcription of RORC while inhibiting transcription of FOXP3, thus favoring differentiation to IL-17-producing helper T cells and inhibiting the differentiation of regulatory T cells. These indoximod-driven effects on CD8+ and CD4+ T cells were independent from the activity of IDO/TDO and from the presence of exogenous Kyn, though they do oppose the effects of Kyn produced by these Trp catabolizing enzymes. Indoximod can also downregulate expression of IDO protein in vivo in murine lymph node dendritic cells and in vitro in human monocyte-derived dendritic cells via a mechanism that involves signaling through the AhR. Together, these data improve the understanding of how indoximod influences the effects of IDO, beyond and distinct from direct enzymatic inhibition of the enzyme.

Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

J Immunother Cancer 2021 Jun;9(6):e002057.PMID:34117113DOI:10.1136/jitc-2020-002057.

Background: The indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma. Methods: Patients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label. Results: Between July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator'S choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P). Conclusion: In this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

Moxibustion alleviates depression-like behavior in rats with Crohn'S disease by inhibiting the kynurenine pathway metabolism in the gut-brain axis

Front Neurosci 2022 Dec 7;16:1019590.PMID:36570839DOI:10.3389/fnins.2022.1019590.

Background: Moxibustion is a potential therapy for inflammatory bowel disease-related depression, but its specific mechanism of action is unclear. This study aimed to investigate the molecular mechanism by which moxibustion alleviates depressive behavior in rats with Crohn'S disease (CD). Methods: The CD rat model was established with 2,4,6-trinitrobenzenesulfonic acid. Treatment with moxibustion was applied to Tianshu (ST25, bilateral), Qihai (CV6), and Baihui (GV20) acupoints, and the effect of moxibustion was compared with that of the combination of moxibustion plus indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, 1-methyltryptophan (1-MT). The effects of moxibustion and moxibustion plus 1-MT combination on colonic inflammation and depressive behavior (assessed by forced swimming test, sucrose preference test, and open field test) were investigated. The changes in IDO1, TNF-α, and IL-1β in rat colon and hippocampus were assessed by Western blot (WB). Gas chromatography-mass spectrometry, immunofluorescence staining, and WB were applied to detect kynurenine pathway (KP) metabolites, hippocampal neuronal activity, and microglia activation, respectively. Results: Both moxibustion and moxibustion plus 1-MT combination significantly alleviated intestinal inflammation and depressive behavior, downregulated the levels of IDO1 in the colon and hippocampus, and inhibited inflammation-inducing factors IL-1β and TNF-α, as well as the kynurenine/tryptophan (KYN/TRP) ratio of KP metabolites, and upregulated the kynurenic acid (KYNA)/KYN ratio and the KYNA/quinolinic acid (QUIN) ratio in the hippocampus in rats with CD; Hippocampal ionized calcium-binding adaptor molecule-1 (Iba-1), c-fos protein expression, activated microglia, and neuronal activation was also significantly reduced by moxibustion and moxibustion plus 1-MT. The addition of 1-MT did not significantly increase the therapeutic effect of moxibustion. Conclusion: Moxibustion can improve depressive behavior in rats with CD, which may be related to its regulation of KP metabolism in the gut-brain axis and inhibition of hippocampal microglia activation and neuronal activation.

IDO-1 inhibition protects against neuroinflammation, oxidative stress and mitochondrial dysfunction in 6-OHDA induced murine model of Parkinson'S disease

Neurotoxicology 2021 May;84:184-197.PMID:33774066DOI:10.1016/j.neuro.2021.03.009.

Parkinson'S disease (PD), a common neurodegenerative motor disorder characterized by striatal dopaminergic neuronal loss and localized neuroinflammation in the midbrain region. Activation of microglia is associated with various inflammatory mediators and Kynurenine pathway (KP) being one of the major regulator of immune response, is involved in the neuroinflammatory and neurotoxic cascade in PD. In the current study, 1-Methyltryptophan (1-MT), an Indolamine-2,3-dioxygenase-1 (IDO-1) inhibitor was tested at different doses (2.5 mg/kg, 5 mg/kg and 10 mg/kg) for its effect on behavioral parameters, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, neurotransmitter levels, biochemical and behavioral alterations in unilateral 6-OHDA (3 μg/μL) murine model of PD. The results showed improved locomotion in open field test and motor coordination in rota-rod, reduced oxidative stress, neuroinflammatory markers (TNF-α, IFN-γ, IL-6), mitochondrial dysfunction and neuronal apoptosis (caspase-3). Also, restoration of neurotransmitter levels (dopamine and homovanillic acid) in the striatum and increased striatal BDNF levels were observed. Overall findings suggest that 1-MT could be a potential candidate for further studies to explore its possibility as an alternative in the pharmacotherapy of PD.