| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| Other Sizes |
| Targets |
The primary target of I2906 is the enzyme isocitrate lyase (ICL) in Mycobacterium tuberculosis. ICL is a key enzyme in the glyoxylate shunt, a pathway essential for the survival and persistence of M. tuberculosis within host macrophages. By inhibiting ICL, I2906 disrupts the bacterium's ability to utilize fatty acids as a carbon source during infection, thereby inhibiting its growth and survival. It is believed to inhibit the synthesis of essential components of the bacterial cell wall, leading to cell death, potentially through the disruption of this metabolic pathway.
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| ln Vitro |
In vitro, I2906 showed excellent antimycobacterial activities against M. tuberculosis. The minimum inhibitory concentration (MIC) was determined to be 134.4 ug/mL against clinical isolates. It has also demonstrated low cytotoxicity in vitro, indicating a favorable selectivity index for the bacterial target. As an isocitrate lyase inhibitor, its activity is linked to the inhibition of the glyoxylate pathway, which is crucial for the persistence of M. tuberculosis. It is also noted to have cytotoxic activity, although this is secondary to its primary antibacterial effect.
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| ln Vivo |
In vivo, I2906 has demonstrated efficacy in a murine model infected with M. tuberculosis. Studies have shown that it can reduce bacterial load in infected animal models. It has shown good activity against M. tuberculosis. Its ability to inhibit the glyoxylate pathway is thought to contribute to its in vivo efficacy. Its activity against M. tuberculosis in animal models supports its potential as a new therapeutic agent for tuberculosis, particularly against persistent infections.
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| Enzyme Assay |
Cell-free enzyme assays for I2906 typically assess its inhibition of isocitrate lyase (ICL). A standard protocol involves incubating recombinant M. tuberculosis ICL with its substrate, isocitrate, and varying concentrations of I2906 in a reaction buffer. The reaction is carried out at 37degC, and the production of glyoxylate and succinate is measured using a coupled enzymatic assay or by high-performance liquid chromatography (HPLC). The IC50 value, representing the concentration of I2906 required for half-maximal enzyme inhibition, is determined from the dose-response curve.
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| Cell Assay |
For in vitro cellular experiments, Mycobacterium tuberculosis cultures are grown in Middlebrook 7H9 medium. Bacteria are treated with I2906 at various concentrations (typically 0.1-100 ug/mL) and incubated at 37degC for several days. The minimum inhibitory concentration (MIC) is determined by visual inspection or by measuring the optical density (OD600) of the culture. To assess cytotoxicity, mammalian cell lines (e.g., Vero cells) are treated with the compound, and cell viability is measured using MTT or resazurin assays.
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| Animal Protocol |
In vivo animal experiments with I2906 are conducted in a murine model of tuberculosis. A common protocol involves infecting mice with M. tuberculosis via aerosol or intravenous injection. After the infection is established, I2906 is administered orally or intraperitoneally at various doses (e.g., 10-100 mg/kg) for several weeks. The compound's efficacy is assessed by measuring the bacterial load (colony-forming units, CFU) in the lungs and spleen of the treated animals compared to untreated controls.
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| ADME/Pharmacokinetics |
I2906 has a molecular weight of 443.6 g/mol and a molecular formula of C25H37N3O4. It is soluble in DMSO at 10 mM. As a small molecule, it is suitable for oral or intraperitoneal administration in animal models. Its pharmacokinetic properties, including absorption, distribution, metabolism, and excretion (ADME), are consistent with a drug-like molecule. It is stored at -20degC, protected from light and moisture, and is stable for long-term storage.
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| Toxicity/Toxicokinetics |
I2906 has demonstrated low cytotoxicity in preclinical studies, suggesting a favorable safety profile. In vitro, it shows excellent antimycobacterial activity with a low toxicity profile. In animal models, it has shown good tolerability at therapeutic doses. However, as with any antimicrobial agent, potential side effects and long-term toxicity need to be evaluated. The compound is for research use only and not for human use. It should be handled with standard laboratory precautions in a biosafety cabinet due to its activity against pathogenic bacteria.
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| References | |
| Additional Infomation |
I2906 is a novel small molecule inhibitor of isocitrate lyase (ICL) with potent antimycobacterial activity against M. tuberculosis. It has shown excellent activity in vitro and in vivo with low cytotoxicity. Its mechanism of action involves inhibiting the glyoxylate pathway, which is essential for the persistence of M. tuberculosis. This makes it a promising candidate for the development of new anti-TB drugs, particularly those aimed at treating persistent and drug-resistant infections.
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| Molecular Formula |
C25H37N3O4
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|---|---|
| Molecular Weight |
443.57898
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| Exact Mass |
443.278
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| CAS # |
331963-29-2
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| PubChem CID |
54679506
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| Appearance |
White to off-white solid powder
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| LogP |
6.214
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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 |
13
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| Heavy Atom Count |
32
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| Complexity |
662
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WIEYSVJHCLJOJT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H37N3O4/c1-3-5-6-7-8-9-10-11-12-13-18-21(29)26-27-24(31)22-23(30)19-16-14-15-17-20(19)28(4-2)25(22)32/h14-17,30H,3-13,18H2,1-2H3,(H,26,29)(H,27,31)
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| Chemical Name |
1-ethyl-4-hydroxy-2-oxo-N'-tridecanoylquinoline-3-carbohydrazide
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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 |
| 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 : ~25 mg/mL (~56.36 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.64 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2544 mL | 11.2719 mL | 22.5438 mL | |
| 5 mM | 0.4509 mL | 2.2544 mL | 4.5088 mL | |
| 10 mM | 0.2254 mL | 1.1272 mL | 2.2544 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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