| Targets |
As a metabolite rather than a therapeutic drug, 1H-Imidazole-4-acetaldehyde does not exert its effects through a dedicated biological receptor. Instead, it directly interacts with specific metabolic enzymes in the body. Its primary interaction is with the enzyme aldehyde dehydrogenase (ALDH), particularly the mitochondrial isoform (ALDH2), which rapidly converts the aldehyde group into a carboxylic acid, yielding imidazoleacetic acid. It can also be generated from histamine by the action of diamine oxidase (DAO). This compound is also recognized as a biomarker for the catabolism of histamine, a critical mediator of immune and allergic responses.
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| ln Vitro |
The biological activity of 1H-Imidazole-4-acetaldehyde is primarily defined by its role in histamine catabolism and its interaction with ALDH enzymes. The conversion of histamine to this metabolite by DAO is a key step in terminating the pro-inflammatory actions of histamine. The subsequent transformation of this compound to imidazoleacetic acid by ALDH is crucial for the efficient elimination of histamine metabolites from the body. In vitro, the compound serves as an excellent substrate for ALDH2, and its presence indicates high histaminase activity. It is not typically cytotoxic but is a reactive molecule due to its aldehyde group, which can form adducts with proteins.
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| ln Vivo |
The in vivo activity of 1H-Imidazole-4-acetaldehyde is intrinsically linked to its role as a pivotal histamine metabolite. It is formed in peripheral tissues where histamine is released, marking the process of histamine inactivation. While it is a normal component of histidine metabolism, its accumulation may be associated with certain disorders. For instance, a defect in its further metabolism is implicated in histidinemia, a rare metabolic disorder characterized by elevated histidine levels. Its concentration in biological fluids is a key indicator used in diagnostic research to assess histamine turnover and metabolic pathway integrity.
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| Enzyme Assay |
General in vitro enzyme assay protocol: A detailed assay protocol typically involves incubating the compound with the target enzyme, aldehyde dehydrogenase (ALDH). In a typical protocol, a reaction mixture containing potassium phosphate buffer (pH 8.0), 0.5 mM NAD+, 1.0 mM pyrazole (to inhibit alcohol dehydrogenase), and varying concentrations of the test compound is pre-incubated for 2 minutes at 25degC. The reaction is initiated by adding ALDH isozymes (e.g., ALDH1A1, ALDH2). The formation of NADH is monitored spectrophotometrically by the increase in absorbance at 340 nm over a 5-10 minute period. The reaction rate is proportional to the ALDH activity.
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| Cell Assay |
General in vitro cell-based metabolism assay: For a cellular assay, a cell line that expresses the key histamine-degrading enzyme diamine oxidase (DAO), such as Caco-2 cells (human intestinal epithelial cells), can be used. Cells are plated in culture medium and allowed to reach confluency. The cells are then treated with a low concentration of histamine (1-10 uM) as a substrate. After a predetermined incubation period (e.g., 1-4 hours), the culture medium is collected. The levels of 1H-Imidazole-4-acetaldehyde produced are quantified by HPLC coupled to a fluorescence detector or LC-MS/MS after derivatization with a suitable agent (e.g., o-phthalaldehyde). Cytotoxicity can be assessed simultaneously via an MTT assay.
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| Animal Protocol |
General in vivo animal protocol for metabolic study: To study histamine metabolism, a pharmacokinetic study can be performed in rodents. Male Sprague-Dawley rats (n=5 per group) are administered a high dose of histamine (e.g., 100 mg/kg, i.p.) to saturate the metabolic pathway. Blood samples are collected at various time points (0, 15, 30, 60, 120 min) from the tail vein. Urine may also be collected in metabolic cages. Plasma and urine samples are deproteinized, and the concentration of 1H-Imidazole-4-acetaldehyde is measured by a validated LC-MS/MS method. The resulting data are used to calculate the formation and elimination kinetics of the metabolite.
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| ADME/Pharmacokinetics |
As a small, polar, and reactive aldehyde (molecular weight 110.1 g/mol, logP approx. -0.5), 1H-Imidazole-4-acetaldehyde is not a conventional drug but a labile endogenous metabolite. If it enters the systemic circulation, it would be rapidly oxidized by ubiquitous aldehyde dehydrogenases, primarily in the liver, to its inactive acid form, imidazoleacetic acid, which would then be excreted renally. Its intrinsic plasma half-life would be extremely short, likely on the order of minutes, as its metabolism is kinetically efficient. It would show low plasma protein binding due to its hydrophilic nature. As a normal part of human metabolism, the parent compound does not accumulate but is processed quickly by the liver. The primary excretion route is renal after conversion to its more stable and water-soluble carboxylic acid metabolite.
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| Toxicity/Toxicokinetics |
As an endogenous metabolite and a normal component of human histamine catabolism, this compound itself is not considered a toxic impurity at physiological levels. However, aldehydes are reactive molecules, and elevated local concentrations can be cytotoxic, contributing to tissue injury. For its use as a chemical reference standard, it is handled as a laboratory reagent with typical safety precautions. It is not classified as a genotoxic impurity under standard pharmaceutical guidelines, as it is a normal metabolic intermediate. The acceptable limit for such an impurity in a drug substance would follow ICH Q3A/B guidelines, typically ≤0.15%, if it were to be present as a contaminant.
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| References | |
| Additional Infomation |
Appearance: Not specified in typical reagent documentation but expected to be a colorless to pale yellow liquid or an oil. Molecular formula: C₅H₆N2O. Molecular weight: 110.11 g/mol. Storage: It is recommended to store the compound at -20degC, under an inert atmosphere (e.g., nitrogen), and protected from light to minimize degradation. Solubility: The compound is expected to be soluble in water and polar organic solvents like DMSO and ethanol. Other names: Imidazol-4-ylacetaldehyde, Imidazole-5-acetaldehyde, 4-Imidazolylacetaldehyde. Safety: As a reactive aldehyde, it should be handled with care in a well-ventilated area, avoiding direct contact with skin and eyes.
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| Exact Mass |
110.048
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|---|---|
| CAS # |
645-14-7
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| PubChem CID |
150841
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| Appearance |
Light yellow to yellow solid-liquid mixture
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
8
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| Complexity |
84.5
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MQSRGWNVEZRLDK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C5H6N2O/c8-2-1-5-3-6-4-7-5/h2-4H,1H2,(H,6,7)
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| Chemical Name |
2-(1H-imidazol-5-yl)acetaldehyde
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| Synonyms |
4-Imidazolylacetaldehyde
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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.) |
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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