| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
The compound is a prodrug of indoximod, which targets the indoleamine 2,3-dioxygenase (IDO) pathway. IDO is an enzyme that catalyzes the rate-limiting step of tryptophan degradation along the kynurenine pathway, leading to immunosuppression in the tumor microenvironment. Indoximod acts as a methylated tryptophan that reverses IDO-mediated tryptophan starvation and downstream signaling, thereby restoring T-cell proliferation and function.
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| ln Vitro |
NLG802 HCl shows increased potency and exposure compared to indoximod. As a prodrug, it is cleaved in vivo to release the active indoximod moiety. The prodrug strategy results in significantly enhanced pharmacokinetic properties, including higher maximum plasma concentration and greater overall systemic exposure, which translates to more effective IDO pathway inhibition and improved immune activation in cancer models.
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| ln Vivo |
Specific in vivo efficacy data for NLG802 HCl are not detailed in the literature; however, the compound is an orally bioavailable prodrug designed to improve upon the in vivo performance of indoximod. Indoximod has shown anti-tumor activity in pre-clinical models and has been evaluated in clinical trials. The enhanced oral bioavailability and exposure of NLG802 HCl are expected to translate into improved anti-tumor immune responses and better efficacy in syngeneic mouse tumor models.
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| Enzyme Assay |
The compound is not an enzyme inhibitor in vitro, as it is a prodrug requiring in vivo conversion. For the active metabolite indoximod, biochemical assays typically involve measuring the conversion of tryptophan to kynurenine by IDO enzyme. Recombinant human IDO is incubated with L-tryptophan, the cofactor methylene blue, and varying concentrations of indoximod (or NLG802 after conversion). The reaction is stopped, and the concentration of L-kynurenine is measured spectrophotometrically at 480 nm after reaction with p-dimethylaminobenzaldehyde (Ehrlich's reagent) to calculate the IC50.
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| Cell Assay |
Cellular IDO activity is assessed using IDO-expressing cells such as HeLa cells (after IFN-gamma stimulation) or monocyte-derived dendritic cells. Cells are seeded in 96-well plates, treated with NLG802 HCl (after conversion to indoximod) or indoximod, and stimulated with IFN-gamma (100 ng/mL) to induce IDO expression. After 24-48 hours, culture supernatants are collected, and kynurenine concentration is measured by LC-MS or colorimetrically. T-cell proliferation assays are performed by co-culturing IDO-expressing dendritic cells with allogeneic CD4+ T cells in the presence of the compound.
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| Animal Protocol |
Specific in vivo protocols for NLG802 HCl are not detailed. A typical efficacy study would use a syngeneic mouse tumor model such as B16-F10 melanoma or 4T1 breast cancer, which are known to express IDO and create an immunosuppressive microenvironment. Mice are inoculated subcutaneously with tumor cells. Once tumors are established (~100-150 mm3), NLG802 HCl is administered orally daily at doses ranging from 50-200 mg/kg. Tumor volume is measured twice weekly. On study termination, tumors are harvested for analysis of infiltrating CD8+ T cells, regulatory T cells (Tregs), and kynurenine/tryptophan ratio by LC-MS.
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| ADME/Pharmacokinetics |
Specific PK parameters for NLG802 HCl are not detailed, but the compound is described as a next-generation IDO pathway inhibitor with increased oral bioavailability and maximum exposure compared to indoximod. The prodrug strategy is designed to overcome the limited oral bioavailability of indoximod (which has a relatively short half-life and low exposure). After oral administration, NLG802 HCl is converted to indoximod, providing higher systemic concentrations of the active metabolite.
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| Toxicity/Toxicokinetics |
Specific toxicological data for NLG802 HCl are not detailed. As a prodrug of indoximod, its safety profile is expected to be similar to or improved over indoximod. Indoximod has been evaluated in clinical trials and is generally well-tolerated, with the most common adverse events being fatigue, nausea, and rash. The IDO pathway is involved in immune regulation at the maternal-fetal interface and in chronic inflammation, but inhibition in adults is not associated with severe toxicities.
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| References | |
| Additional Infomation |
Indoximod has been investigated in numerous clinical trials for various cancers, including melanoma, pancreatic cancer, and glioblastoma, often in combination with checkpoint inhibitors (e.g., pembrolizumab, nivolumab). NLG802 HCl is a research-grade prodrug designed to overcome the bioavailability limitations of indoximod. As of the latest updates, it is exclusively available for pre-clinical research and has not yet been approved for clinical use, representing an improved tool for studying the IDO pathway in cancer immunotherapy.
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| Molecular Formula |
C20H30CLN3O3
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|---|---|
| Molecular Weight |
395.92350435257
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| Exact Mass |
395.197
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| CAS # |
2071683-99-1
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| Related CAS # |
2071684-08-5;2071684-09-6 (HCl);2071683-99-1
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| PubChem CID |
162623745
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
27
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| Complexity |
483
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| Defined Atom Stereocenter Count |
2
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| SMILES |
Cl.O(CC)C([C@@H](CC1=CN(C)C2C=CC=CC1=2)NC([C@H](CC(C)C)N)=O)=O
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| InChi Key |
PXFDVONNVFXYEP-MCJVGQIASA-N
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| InChi Code |
InChI=1S/C20H29N3O3.ClH/c1-5-26-20(25)17(22-19(24)16(21)10-13(2)3)11-14-12-23(4)18-9-7-6-8-15(14)18;/h6-9,12-13,16-17H,5,10-11,21H2,1-4H3,(H,22,24);1H/t16-,17+;/m0./s1
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| Chemical Name |
ethyl (2R)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-(1-methylindol-3-yl)propanoate;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO : ~250 mg/mL (~631.44 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5258 mL | 12.6288 mL | 25.2576 mL | |
| 5 mM | 0.5052 mL | 2.5258 mL | 5.0515 mL | |
| 10 mM | 0.2526 mL | 1.2629 mL | 2.5258 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.
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