| Size | Price | Stock | Qty |
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| 500mg |
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| 1g |
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| 2g |
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| 5g | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Indoximod targets IDO1 (Indoleamine 2,3-dioxygenase 1) [1]
Indoximod targets IDO1 (mediating mTOR pathway regulation via tryptophan sufficiency signal) [2] |
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| ln Vitro |
One-methyl-tryptophan, an IDO inhibitor, comes in two stereoisomers, each of which may have distinct pharmacological characteristics. In studies utilizing HeLa cells and the pure enzyme, the L isomer exhibits greater potency as an inhibitor of IDO activity. On the other hand, the inhibition of T cells caused by dendritic cells expressing IDO is considerably more effectively reversed by the D isomer. The competitive inhibitory action of 1-methyl-tryptophan was observed for the L isomer (Ki=19 μM), while the d isomer exhibited significantly lower efficacy. The DL combination has a Ki of 35 μM, making it intermediate[1].
IDO enzyme activity inhibition: Indoximod concentration-dependently inhibited IDO activity in LPS-stimulated dendritic cells, reducing kynurenine (Kyn) production and increasing the tryptophan (Trp)/Kyn ratio in cell supernatants [1] - T cell activation promotion: When co-cultured with Indoximod-treated dendritic cells, allogeneic T cells showed enhanced proliferation and increased secretion of pro-inflammatory cytokines (e.g., IFN-γ), while anti-inflammatory cytokine (e.g., IL-10) production was reduced [1] - mTOR pathway activation: Indoximod reversed IDO-mediated mTOR pathway suppression in tumor cells and immune cells, increasing the expression levels of phosphorylated mTOR (p-mTOR) and phosphorylated S6K1 (p-S6K1) [2] - Cell proliferation regulation: Indoximod promoted the proliferation of immune cells and inhibited the survival of tumor cells in vitro [2] |
| ln Vivo |
Tested in mouse models of transplantable melanoma and transplantable and autochthonous breast cancer, the D isomer is more effective as an anticancer agent in chemo-immunotherapy regimens using NSC-26271, NSC 125973, or LY 188011. Since mice with an IDO gene disruption (IDO-knockout mice) completely lose the antitumor effect of d-1-methyl-tryptophan, the D isomer of 1-methyl-tryptophan specifically targets the IDO gene. When combined with NSC 125973, oral dl-1-methyl-tryptophan administration has been shown to cause autochthonous breast tumor regression[1].
Antitumor efficacy: Indoximod significantly suppressed tumor growth and reduced tumor weight in mouse subcutaneous xenograft models, with increased infiltration of CD4+ and CD8+ T cells in tumor tissues [1] - Immune microenvironment improvement: Indoximod decreased the proportion of regulatory T cells (Treg) in tumor tissues and enhanced IFN-γ secretion, alleviating immune suppression [1] - Survival extension: Indoximod (alone or in combination with other therapies) prolonged the survival of tumor-bearing mice and activated the mTOR pathway in tumor tissues [2] |
| Enzyme Assay |
IDO enzyme activity detection: Prepare recombinant IDO protein or dendritic cell lysate as the enzyme source, add tryptophan as the substrate, and incubate with different concentrations of Indoximod at an appropriate temperature for a certain period. Detect the production of kynurenine (the metabolite of tryptophan) using chromatographic or spectrophotometric methods to calculate the inhibition rate of IDO enzyme activity [1]
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| Cell Assay |
Dendritic cell-T cell co-culture assay: Culture bone marrow-derived dendritic cells, induce IDO expression with LPS stimulation, and treat with Indoximod. After incubation, detect IDO protein expression in cells and the concentrations of tryptophan and kynurenine in supernatants. Co-culture treated dendritic cells with allogeneic T cells, and analyze T cell proliferation and cytokine secretion by flow cytometry [1]
- mTOR pathway detection assay: Culture tumor cells or immune cells, treat with Indoximod, extract total cellular protein, and detect the expression levels of mTOR pathway-related proteins (p-mTOR, p-S6K1) by western blot. Evaluate cell proliferation activity using CCK-8 or BrdU incorporation assay [2] |
| Animal Protocol |
Dissolved in 0.5% Tween 80/0.5% Methylcellulose (v/v) in water; 400 mg/kg; p.o. administration
Mouse B16F10 and 4T1 tumor models Tumor xenograft model assay (Study [1]): Subcutaneously inoculate tumor cells into the right back of mice to establish xenograft models. When tumors reach a certain volume, randomly divide mice into groups. Administer Indoximod to experimental groups via intraperitoneal injection or oral gavage once daily for a continuous period. Regularly measure tumor volume during the experiment; after sacrifice, weigh tumor tissues and analyze immune cell infiltration in tumors and spleens [1] - mTOR pathway-related in vivo assay (Study [2]): Establish mouse tumor models, administer Indoximod (alone or in combination) according to experimental design. After treatment, detect tumor growth and survival time of mice. Collect tumor tissues and immune organs to detect mTOR pathway protein expression and immune cell infiltration via immunohistochemistry or western blot [2] |
| References |
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| Additional Infomation |
Indoximod is an indole carboxylic acid. Indomod has been used in therapeutic trials for various cancers, including glioma, melanoma, ependymoma, gliosarcoma and lung cancer. Indomod is a methylated tryptophan with immune checkpoint inhibitory activity. Indomod inhibits indoleamine 2,3-dioxygenase (IDO), an enzyme that degrades the essential amino acid tryptophan, and therefore indomod may increase or maintain tryptophan levels that are crucial for T cell function. Tryptophan depletion is associated with immunosuppression, including T cell arrest and unresponsiveness. Mechanism of action (studies [1]): Indomod is a stereoisomer of D-1-methyltryptophan. It specifically inhibits IDO enzyme activity, blocks the metabolism of tryptophan to kynurenine, relieves IDO-mediated immunosuppression, and restores the antitumor immune function of T cells [1]. - Novel effector pathway (studies [2]): IDO inhibits the mTOR pathway by inhibiting tryptophan sufficiency signaling. Indoximod reversed this inhibitory effect, enhanced the activation and proliferation of immune cells, and exerted its antitumor effect through this additional mechanism [2]
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| Molecular Formula |
C12H14N2O2
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| Molecular Weight |
218.25
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| Exact Mass |
218.105
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| CAS # |
110117-83-4
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| Related CAS # |
(Rac)-Indoximod;26988-72-7;(S)-Indoximod;21339-55-9
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| PubChem CID |
405012
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
429.3±35.0 °C at 760 mmHg
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| Melting Point |
242-245 ℃(lit.)
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| Flash Point |
213.4±25.9 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.625
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| LogP |
1.43
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
16
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| Complexity |
270
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1C=C(C2=CC=CC=C21)C[C@H](C(=O)O)N
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| InChi Key |
ZADWXFSZEAPBJS-SNVBAGLBSA-N
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| InChi Code |
InChI=1S/C12H14N2O2/c1-14-7-8(6-10(13)12(15)16)9-4-2-3-5-11(9)14/h2-5,7,10H,6,13H2,1H3,(H,15,16)/t10-/m1/s1
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| Chemical Name |
(2R)-2-amino-3-(1-methylindol-3-yl)propanoic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (4.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.5819 mL | 22.9095 mL | 45.8190 mL | |
| 5 mM | 0.9164 mL | 4.5819 mL | 9.1638 mL | |
| 10 mM | 0.4582 mL | 2.2910 mL | 4.5819 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01560923 | Completed Has Results | Biological: Indoximod Biological: Sipuleucel-T |
Metastatic Prostate Cancer | Masonic Cancer Center, University of Minnesota |
October 1, 2012 | Phase 2 |
| NCT02835729 | Completed | Drug: Cytarabine Drug: Indoximod Freebase |
Acute Myeloid Leukemia | NewLink Genetics Corporation | July 2016 | Phase 1 |
| NCT02502708 | Completed | Drug: Indoximod Drug: Temozolomide |
Glioblastoma Multiforme Glioma |
NewLink Genetics Corporation | October 2015 | Phase 1 |
| NCT02077881 | Completed | Drug: Gemcitabine Drug: Indoximod |
Metastatic Pancreatic Adenocarcinoma | NewLink Genetics Corporation | August 2014 | Phase 1 Phase 2 |
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