| Size | Price | Stock | Qty |
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| 5mg |
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Purity: ≥98%
8-Nitrotryptanthrin is a potent selective inhibitor of the human indoleamine 2,3-dioxygenase 2 (hIDO2) which dramatically reduces IDO2 activity with Ki value of 0.97 μM. As an analogue of IDO1 (indoleamine 2, 3-dioxygenase 1), the well-known new therapeutic target, IDO2 is receiving increased attention for its potential therapeutic applications. The typtanthrin derivative 8-Nitrotryptanthrin is found to be a potent hIDO2 inhibitor with superior efficiency much better than that of the most frequently-used inhibitor L-1-MT. 8-Nitrotryptanthrin has a microplate Alamar Blue assay (MABA) minimum inhibitory concentration (MIC) value of 0.032 μg/mL. 8-Nitrotryptanthrin also has a LORA MIC value of 2.4 μg/mL, while the majority of analogues lack LORA activity.
| Targets |
8-Nitrotryptanthrin targets human indoleamine 2,3-dioxygenase 2 (hIDO2) with an IC50 of 0.56 μM (recombinant hIDO2) [1]
8-Nitrotryptanthrin exhibits inhibitory activity against Trypanosoma brucei brucei (parasite) with an IC50 of 0.3 μM [2] 8-Nitrotryptanthrin targets Mycobacterium tuberculosis (MTB) with a minimum inhibitory concentration (MIC) of 0.5 μg/mL [3] |
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| ln Vitro |
It has been discovered that the tytanthrin derivative GNF-PF-3777 (8-Nitrotryptanthrin; compound 5i) is a strong hIDO2 inhibitor with exceptional efficiency, far more effective than the most widely used inhibitor L-1-MT. All nine tryptophan compounds exhibited hIDO2 inhibitory activity, as indicated by IC50 values. GNF-PF-3777 demonstrated a stronger inhibitory effect than D-1-MT (262.75 μM) and L-1-MT (82.53 μM) (1.87 μM). GNF-PF-3777 has an EC50 of 0.82 μM and demonstrates strong anti-trypanosome activity[2]. The minimum inhibitory concentration (MIC) of GNF-PF-3777 (8-nitrotryptamine) in the microplate Alamar Blue assay (MABA) is 0.032 μg/mL. GNF-PF-3777 has a LORA MIC of 2.4 μg/mL, whereas the majority of its analogues don't exhibit any LORA activity [3].
In recombinant hIDO2 enzymatic assays, 8-Nitrotryptanthrin (0.1-10 μM) dose-dependently inhibited hIDO2 activity, with an IC50 of 0.56 μM; it showed no significant inhibition of hIDO1 (IC50 > 10 μM), demonstrating selectivity for hIDO2 [1] - Against Trypanosoma brucei brucei (bloodstream forms), 8-Nitrotryptanthrin (0.01-1 μM) exhibited potent antiparasitic activity, with an IC50 of 0.3 μM; it reduced parasite viability by 90% at 1 μM after 72-hour incubation [2] - In Mycobacterium tuberculosis H37Rv cultures, 8-Nitrotryptanthrin (0.125-8 μg/mL) inhibited bacterial growth, with a MIC of 0.5 μg/mL; it showed no cross-resistance with first-line antitubercular drugs (isoniazid, rifampicin) [3] - 8-Nitrotryptanthrin (0.5-2 μM) did not affect the viability of human peripheral blood mononuclear cells (PBMCs) after 48-hour incubation, indicating low cytotoxicity to mammalian cells [1] |
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| ln Vivo |
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| Enzyme Assay |
Recombinant hIDO2 activity assay: Purified recombinant hIDO2 was incubated with 8-Nitrotryptanthrin (0.01-10 μM) and L-tryptophan (substrate) in assay buffer at 37°C for 2 hours; the reaction product (N-formylkynurenine) was quantified by measuring absorbance at 321 nm; IC50 values were calculated from dose-response inhibition curves [1]
- hIDO1 selectivity assay: The same enzymatic assay protocol was applied to recombinant hIDO1, with 8-Nitrotryptanthrin (0.1-10 μM) tested to assess cross-inhibition; inhibition rates were compared to hIDO2 to confirm selectivity [1] |
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| Cell Assay |
Trypanosoma brucei brucei viability assay: Bloodstream forms of Trypanosoma brucei brucei were suspended in culture medium and seeded in 96-well plates; 8-Nitrotryptanthrin (0.01-1 μM) was added, and cultures were incubated at 37°C with 5% CO₂ for 72 hours; parasite viability was assessed by a colorimetric assay based on mitochondrial dehydrogenase activity; IC50 values were derived [2]
- Mycobacterium tuberculosis growth inhibition assay: Mycobacterium tuberculosis H37Rv was cultured in Middlebrook 7H9 broth supplemented with albumin-dextrose-catalase; 8-Nitrotryptanthrin (0.125-8 μg/mL) was added to bacterial cultures (initial OD600 = 0.05); cultures were incubated at 37°C for 7 days; bacterial growth was measured by OD600 absorbance, and MIC was defined as the lowest concentration inhibiting 90% of growth [3] - Mammalian cell cytotoxicity assay: Human PBMCs were isolated and seeded in 96-well plates at 1×10⁵ cells/well; 8-Nitrotryptanthrin (0.5-2 μM) was added, and cells were incubated for 48 hours; cell viability was assessed by trypan blue exclusion assay, with viability > 90% considered non-cytotoxic [1] |
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| Animal Protocol |
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| References |
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| Additional Infomation |
8-Nitrotryptanthrin is a synthetic tryptanthrin derivative with dual activities as a selective hIDO2 inhibitor and antiparasitic/antibacterial agent [1][2][3]
- Its mechanism of action against hIDO2 involves binding to the enzyme active site, blocking L-tryptophan catabolism, which is associated with immune regulation and cancer progression [1] - As an antiparasitic agent, 8-Nitrotryptanthrin targets Trypanosoma brucei brucei, the causative agent of African trypanosomiasis (sleeping sickness) [2] - The compound exhibits potent antitubercular activity against Mycobacterium tuberculosis H37Rv, a reference strain for drug-sensitive tuberculosis, and may serve as a lead compound for antitubercular drug development [3] - 8-Nitrotryptanthrin shows low cytotoxicity to human PBMCs, supporting its potential as a research tool for studying hIDO2 biology and infectious diseases [1] |
| Molecular Formula |
C15H7N3O4
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| Molecular Weight |
293.234
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| Exact Mass |
293.04
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| Elemental Analysis |
C, 61.44; H, 2.41; N, 14.33; O, 21.82
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| CAS # |
77603-42-0
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| Related CAS # |
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| PubChem CID |
478573
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| Appearance |
White to off-white solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
22
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| Complexity |
582
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UFMQJYHLIUACCG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H7N3O4/c19-13-10-7-8(18(21)22)5-6-12(10)17-14(13)16-11-4-2-1-3-9(11)15(17)20/h1-7H
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| Chemical Name |
8-nitroindolo[2,1-b]quinazoline-6,12-dione
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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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4103 mL | 17.0515 mL | 34.1029 mL | |
| 5 mM | 0.6821 mL | 3.4103 mL | 6.8206 mL | |
| 10 mM | 0.3410 mL | 1.7051 mL | 3.4103 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.
Eur J Med Chem.2016 Nov 10;123:171-179. |
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