Indoximod (NLG-8189)
(Synonyms: 1-甲基-D-色氨酸,1-Methyl-D-tryptophan; NLG-8189) 目录号 : GC11066
An inhibitor of indoleamine 2,3-dioxygenase
Cas No.:110117-83-4
Sample solution is provided at 25 µL, 10mM.
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Indoximod is an Indoleamine 2,3-dioxygenase (IDO) pathway inhibitor. IDO is a tryptophan-catabolizing enzyme that tumors use to create a state of immunosuppression. [1]
The immunosuppressive activity of IDO leads to an increase in the number of T-regulatory cells, as measured by their Foxp3+/CD4+/CD25+ phenotype. Indoximod has also been shown to reduce the number of T-regulatory cells [2]. In MMTV-Neu mice, researchers looked at the activity of indoximod with and without paclitaxel [3]. The combination of docetaxel and indoximod is more toxic than docetaxel monotherapy. A single 1200 mg dose of indoximod almost totally saturates the gut, and higher doses do not significantly increase peak serum levels. The single-agent phase I trial of indoximod demonstrated very good oral bioavailability and a mild toxicity profile with no significant myelosuppression, and no maximally tolerated dose was identified up to 2000 mg orally twice daily [1].
Blockade of IDO with indoximod enhanced the adoptive immunologic response to antigens and dendritic cell (DC) vaccines in LLC mouse models.
References:
[1]. Soliman HH, Jackson E, Neuger T et al. A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors. Oncotarget. 2014 Sep 30;5 (18):8136-46.
[2]. Munn DH. Blocking IDO activity to enhance anti-tumor immunity. Front Biosci (Elite Ed). 2012 Jan 1;4:734-45.
[3]. Muller AJ, DuHadaway JB, Donover PS et al.Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med. 2005 Mar;11(3):312-9. Epub 2005 Feb 13.
| Cell experiment [1]: | |
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Cell lines |
Treg cells |
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Preparation method |
The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0.05 mM |
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Applications |
Indoximod significantly inhibited the differentiation of Treg cells, especially that of IL-10+ Treg cells, whilst showed no effect on TGF-β1+ Treg cells. Treg cells co-cultured with Indoximod-pretreated ESCs exhibited less suppressive function. The results indicated that indoleamine 2,3-dioxygenase-1 (IDO1) was involved in the differentiation and suppressive function of Treg cells in endometriosis. |
| Animal experiment [2]: | |
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Animal models |
Mice bearing 4T1 tumors |
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Dosage form |
400 mg/kg; p.o.; b.i.d., 5 times a week |
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Applications |
In mice bearing 4T1 tumors, DL-Indoximod in combination with Cyclophosphamide enhanced antitumor immunity. In addition, the drug combination induced a marked decrease in tumor size. Compared with the combination of L-Indoximod and Cyclophosphamide, D-Indoximod combined with Cyclophosphamide significantly prolonged the survival period. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Wei C, Mei J, Tang L, Liu Y, Li D, Li M, Zhu X. 1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis. Cell Death Dis. 2016 Dec 1;7(12):e2489. [2]. Hou DY, Muller AJ, Sharma MD, DuHadaway J, Banerjee T, Johnson M, Mellor AL, Prendergast GC, Munn DH. Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses. Cancer Res. 2007 Jan 15;67(2):792-801. | |
| Cas No. | 110117-83-4 | SDF | |
| 别名 | 1-甲基-D-色氨酸,1-Methyl-D-tryptophan; NLG-8189 | ||
| 化学名 | (E)-3'-methyl-3''-styryl-3,2':5',2'':5'',3'''-quaterpyridine | ||
| Canonical SMILES | OC([C@H](N)CC1=CN(C)C2=CC=CC=C21)=O | ||
| 分子式 | C12H14N2O2 | 分子量 | 218.25 |
| 溶解度 | ≥ 1.12mg/mL in Water with ultrasonic and warming, <2.18mg/mL in DMSO | 储存条件 | Store at -20°C |
| 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。 |
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| 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。 | ||
| 制备储备液 | |||
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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 |
| 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 | 只 |
| 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 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet