| Size | Price | |
|---|---|---|
| 1mg | ||
| Other Sizes |
| Targets |
Endogenous metabolite; itaconic acid targets isocitrate lyase (ICL, in bacteria), succinate dehydrogenase (SDH), and activates Nrf2 via Keap1 alkylation. Modulates pentose phosphate pathway (PPP) by inhibiting 6-phosphogluconate dehydrogenase (6PGD). Endogenous immunometabolite linking immune activation to metabolic reprogramming, with anti-inflammatory and antibacterial activities.
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| ln Vitro |
As 13C-labeled internal standard, itaconic acid-13C5 is not biologically active. Unlabeled itaconic acid is produced by activated macrophages via IRG1 (ACOD1). Exhibits anti-inflammatory activity by inhibiting SDH (IC50 ~10-30 uM) and activating Nrf2, leading to antioxidant gene expression (HO-1, NQO1). Antibacterial against M. tuberculosis (MIC 1-5 mM) by inhibiting isocitrate lyase (ICL), a key enzyme of the glyoxylate cycle. Promotes PPP, increasing NADPH and ROS.
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| ln Vivo |
Itaconic acid is an endogenous immunometabolite produced by activated macrophages in response to bacterial infection, playing a crucial protective role. In mouse LPS-induced septic shock, cell-permeable 4-octyl itaconate (4-OI) reduces serum TNF-alpha and IL-6 and improves survival. In DSS colitis and ischemia-reperfusion injury, itaconate reduces inflammation and tissue damage via Nrf2-dependent antioxidant responses. Itaconic acid-13C5 is used as internal standard to quantify endogenous itaconic acid in these models.
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| Enzyme Assay |
No specific binding for labeled compound. For LC-MS/MS of itaconic acid: (1) Prepare calibration standards in blank matrix with unlabeled itaconic acid (0.1-1000 ng/mL) and fixed concentration of itaconic acid-13C5 (50-500 ng/mL). (2) Add 3-5 vol ice-cold 80% methanol containing IS to 50-100 uL sample. (3) Centrifuge, evaporate, reconstitute in 0.1% formic acid in water. (4) HILIC or C18 column with ion-pairing, ESI- MRM m/z 129→85 (itaconic acid), m/z 134→90 (itaconic acid-13C5).
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| Cell Assay |
(1) For cellular labeling: seed RAW 264.7 macrophages in 6-well plates. (2) Add itaconic acid-13C5 (10-500 uM) for 6-24 h. (3) Harvest cells, extract with 80% ice-cold methanol, analyze by LC-MS/MS to study uptake and metabolism. (4) For endogenous itaconic acid: stimulate RAW 264.7 cells with LPS (1 ug/mL) for 6-24 h, harvest, extract with 80% methanol containing itaconic acid-13C5 as IS, quantify by LC-MS/MS.
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| Animal Protocol |
(1) For metabolic studies: use 6-8 week old male C57BL/6 mice (20-25 g). (2) For LPS-induced endotoxemia: inject LPS (5-10 mg/kg IP) to induce itaconic acid production. (3) Collect blood and tissues (liver, lung, spleen) at 0,2,6,12,24 h. (4) To 50-100 uL plasma or 50-100 mg tissue, add 5 vol 80% methanol containing itaconic acid-13C5 as IS. (5) Homogenize tissues, centrifuge, analyze supernatant by LC-MS/MS. (6) Quantify endogenous itaconic acid in plasma and tissues. (7) For PK of itaconic acid or 4-OI: administer compound (50-200 mg/kg IP), collect plasma, add itaconic acid-13C5 IS, analyze by LC-MS/MS.
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| ADME/Pharmacokinetics |
Soluble in water (≥50 mg/mL) and 80% methanol. For IS, prepare stock in water or 80% methanol at 0.5-1 mg/mL. For LC-MS, dilute to 10-1000 ng/mL in 80% methanol. Storage: powder at -20degC for 3 years; solution at -20degC for 6 months, -80degC for 1 year. 13C label does not alter chemical properties.
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| Toxicity/Toxicokinetics |
Itaconic acid-13C5 is a stable isotope-labeled internal standard used at trace levels, non-toxic. Unlabeled itaconic acid is an endogenous metabolite with excellent safety profile. In vitro: itaconic acid 0.5-10 mM in RAW 264.7 or HEK293 cells shows no significant cytotoxicity; IC50 >20 mM. In vivo: MTD of 4-OI in mice >500 mg/kg IP; repeated 100 mg/kg IP daily for 7 days well tolerated. For research only.
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| References | |
| Additional Infomation |
Itaconic acid-13C5 is a high-purity stable isotope-labeled (13C-labeled) internal standard for accurate quantification of itaconic acid by GC-MS or LC-MS. Itaconic acid is an endogenous immunometabolite produced by activated macrophages via cis-aconitate decarboxylase (IRG1, ACOD1). Plays crucial role in immunometabolism, linking immune activation to metabolic reprogramming. Has anti-inflammatory (inhibiting SDH, activating Nrf2) and antibacterial (inhibiting isocitrate lyase) properties. Elevated in activated macrophages and in response to bacterial infection, inflammation, oxidative stress. Used in studies of sepsis, inflammatory diseases, cancer, and metabolic disorders. Not a drug; strictly for research use.
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| Molecular Formula |
C5H6O4
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|---|---|
| Molecular Weight |
135.062016010284
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| Exact Mass |
135.043
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| CAS # |
2095777-38-9
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| Related CAS # |
Itaconic acid;97-65-4
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| PubChem CID |
162342694
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| Appearance |
White to off-white solid powder
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| LogP |
-0.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
9
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| Complexity |
158
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O[13C]([13CH2][13C](=[13CH2])[13C](=O)O)=O
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| InChi Key |
LVHBHZANLOWSRM-CVMUNTFWSA-N
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| InChi Code |
InChI=1S/C5H6O4/c1-3(5(8)9)2-4(6)7/h1-2H2,(H,6,7)(H,8,9)/i1+1,2+1,3+1,4+1,5+1
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| Chemical Name |
2-(113C)methylidene(1,2,3,4-13C4)butanedioic acid
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 7.4041 mL | 37.0206 mL | 74.0412 mL | |
| 5 mM | 1.4808 mL | 7.4041 mL | 14.8082 mL | |
| 10 mM | 0.7404 mL | 3.7021 mL | 7.4041 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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