1H-1,2,4-Triazol-3-amine functions as a small molecule irreversible inhibitor of catalase. Catalase is an enzyme that catalyzes the decomposition of hydrogen peroxide (H2O2) to water and oxygen, protecting cells from oxidative damage. By inhibiting catalase, the compound increases cellular H2O2 levels, which can have various biological effects, including the induction of oxidative stress and the modulation of redox signaling pathways. The compound is also used as a starting material for the synthesis of antifungals, anticancer drugs, and inhibitors of enzymes associated with cardiovascular disease. Its triazole ring and amino group provide a scaffold for the synthesis of various biologically active molecules. In plants, the compound blocks the formation of 18S Fraction I protein, chloroplast DNA, and 70S ribosomes, and inhibits riboflavin biogenesis.

For life science-related study, 1H-1,2,4-Triazol-3-amine is a biochemical reagent that can be utilized as an organic substance or biological material.

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In vitro, 1H-1,2,4-triazol-3-amine is used as a catalase inhibitor. It is used as a starting material for the synthesis of pharmaceutical compounds, such as antifungals, anticancer drugs, and inhibitors of enzymes associated with cardiovascular disease. In agrochemicals, it is used as a herbicide. The compound blocks the formation of 18S Fraction I protein, chloroplast DNA, and 70S ribosomes, and inhibits riboflavin biogenesis. In medicinal chemistry, it serves as a precursor for the synthesis of various pharmaceutical agents. Its triazole ring provides a scaffold for the synthesis of diverse biologically active molecules.

In vivo, 1H-1,2,4-triazol-3-amine is used as a herbicide in agricultural applications. Its catalase inhibitory activity may have implications for oxidative stress and redox signaling in vivo. However, specific in vivo studies on the compound as a therapeutic agent are limited. The compound's use as a starting material for pharmaceuticals means that its derivatives may be evaluated in animal models for therapeutic efficacy.

Cell-free assays for 1H-1,2,4-triazol-3-amine involve studying its catalase inhibitory activity. The compound is incubated with catalase enzyme and hydrogen peroxide, and the rate of H2O2 decomposition is measured spectrophotometrically. The compound's ability to inhibit catalase is assessed by comparing the rate of H2O2 decomposition in the presence and absence of the compound. Its use as a starting material for pharmaceutical synthesis involves standard organic synthesis procedures.

Cellular assays for 1H-1,2,4-triazol-3-amine involve treating cells with the compound and measuring catalase activity and H2O2 levels. Cells are treated with the compound at various concentrations, and catalase activity is measured using standard assays. H2O2 levels are measured using fluorescent probes such as DCFH-DA. The compound's effects on oxidative stress and cell viability are assessed. Its derivatives may be evaluated in cell-based systems for antifungal, anticancer, or cardiovascular activities.

Animal studies for 1H-1,2,4-triazol-3-amine are primarily related to its use as a herbicide. The compound's catalase inhibitory activity may have implications for oxidative stress and redox signaling in vivo, but specific therapeutic studies are limited. Its derivatives may be evaluated in animal models for antifungal, anticancer, or cardiovascular efficacy.

Absorption, Distribution and Excretion
Aminotriazole was applied to rabbit skin. Within 15 minutes, aminotriazole had entered the bloodstream. Storage sites in adipose tissue were negligible. Wistar rats were administered 1 mg of 14C-aminotriazole (per rat) via gavage. Radioactivity in exhaled breath, urine, feces, and tissues was analyzed within three days post-administration. In the first 24 hours, 70% to 95.5% of the radioactivity was present in urine; trace amounts were also detected in feces. After absorption, aminotriazole was distributed throughout most body tissues. The highest radioactivity was observed in the liver and kidneys. Radioactivity levels in tissues began to decrease within three to four hours post-administration. Paper chromatography analysis showed the presence of both unmetabolized amitraline and an unidentified metabolite in rat liver sections collected at different time points post-administration. The main routes of exposure are skin contact, eye contact, and inhalation of powders, liquids, and aerosols.
Anesthetized animals inhaled a liquid aerosol of drug solution generated by an aerosol nebulizer via endotracheal intubation. The median mass aerodynamic diameter of the aerosol was 2.81 μm, with a geometric standard deviation of 2.53. The time required for 50% absorption of amitraline was 1.3 minutes. Compared with the previously reported absorption rate measured after intratracheal injection of 0.1 mL of drug solution, the absorption rate of the inhaled aerosol was approximately twice that of intratracheal injection.
For more complete data on absorption, distribution, and excretion of AMITROLE (11 species), please visit the HSDB record page.

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Metabolism/Metabolites
A 39-year-old woman ingested 20 mg/kg aminotriazole, and several hours later, urine samples contained unmetabolized aminotriazole (100 mg/100 mL). No metabolites were found.
Plant Metabolism: Glycine and serine in plants are used for the biosynthesis of β-(3-amino-S-triazolyl-1-)α-alanine.
Three compounds were observed in the study of Canada thistle. One of them was identified as β-(3-amino-1,2,4-triazolyl-1)-α-alanine.
The main metabolite produced by amitrole during microbial activity is carbon dioxide. E. coli converts 3-ATA into the metabolite 3-amino-1,2,4-triazolylalanine.
For more complete metabolite/metabolite data on amitrole (10 metabolites in total), please visit the HSDB record page.

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Biological Half-Life
Five male and five female Sprague-Dawley rats (weighing 200–250 g each) were exposed to 5-14C-aminotriazole (radiochemical purity > 97%) water aerosol at concentrations of 49.2 μg/L (2.6 μCurie/L) or 25.8 μg/L (1.4 μCurie/L) (nasal or systemic exposure only) for 1 hour, followed by observation for 120 hours. The particle size distribution of the aerosol was not reported. The elimination half-life of the radioactive material was calculated to be approximately 21 hours under both exposure methods; approximately 75% of the radioactive material was excreted in the urine within 12 hours.

Rats (5 males and 5 females; Charles River Laboratory) were exposed to radiolabeled amitraro via inhalation. The estimated systemic exposure dose was 25.8 μg/L, and the estimated head exposure dose was 49.2 μg/L, for a duration of 1 hour. Blood samples were collected at specified time intervals, and radioactivity was detected in urine, feces, and cadavers. ...The plasma half-life was estimated to be 20 hours.

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Pharmacokinetic data for 1H-1,2,4-triazol-3-amine are not well characterized. As a small polar molecule with a molecular weight of 84.08 g/mol, it is expected to have high bioavailability if administered. However, comprehensive pharmacokinetic studies have not been performed, as the compound is primarily a research reagent and herbicide. For research purposes, the compound is typically handled as a neat chemical and not administered to living organisms for pharmacokinetic profiling.

Toxicity Data
LC50 >500 mg/m3

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Interactions ... Effects of the two inhibitors on rats... Effects on the oxidation of methanol and ethanol to carbon dioxide, and on the in vitro activities of rat liver alcohol dehydrogenase and catalase. ... 3-Amino-1,2,4-triazole significantly reduced... the amount of carbon dioxide produced from methanol... and slightly reduced the amount of carbon dioxide produced from ethanol. ... There was an additive effect when used concurrently with pyrazole...
Administration of 3-amino-1,2,4-triazole (AT) at 3 and 6 hours resulted in the formation of small, round vesicles in the rough endoplasmic reticulum, ribosome shedding, the appearance of large areas of smooth endoplasmic reticulum, the appearance of elongated and deformed mitochondria, and an increase in the number of peroxisomes. Administration of carbon tetrachloride to animals pretreated with AT caused the effects of AT on the reticulum to cancel each other out and prevented myelin formation.
Mercury transport in the placenta of pregnant mice and its localization in the embryo and fetus from early organogenesis to the entire fetal period were investigated using whole-body autoradiography and gamma counting. Pre-administration of aminotriazole to the mother mice resulted in increased mercury concentrations in the fetus (particularly in the liver) after inhalation of mercuric oxide, but this was not observed after injection of (2+) mercury ions.
Mercury accumulated in multiple organs after inhalation of radioactive metallic mercury vapor in mice, but no organ-specific absorption was observed after intravenous injection of inorganic mercury. Ethanol and aminotriazole (a catalase inhibitor) reduced mercury concentrations in some of these organs, but the reduction patterns were not entirely the same. In the livers of untreated animals, most of the inhaled mercury accumulated in hepatocytes in the perilobular region (periportal region), near where blood vessels enter the hepatic parenchyma. Aminotriazole treatment increased hepatic mercury content, and almost all hepatocytes appeared to be involved in the oxidation of mercuric oxide.
For more complete data on interactions with AMITROLE (9 items in total), please visit the HSDB records page.

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Non-human toxicity values
Oral LD50 in mice: 14.7 g/kg
Oral LD50 in rats: 25 g/kg
Oral LD50 in mice: 11,000 mg/kg
Inhalation LC50 in mice: 439 mg/m³/4 hours
For more complete (11) non-human toxicity values for AMITROLE, please visit the HSDB records page.

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Toxicological data for 1H-1,2,4-triazol-3-amine indicate that it is used as a herbicide and may have toxicity at high doses. The compound is classified as a potential carcinogen and may cause skin and eye irritation. Appropriate safety precautions should be taken when handling the compound, including the use of personal protective equipment such as gloves and safety goggles. The compound should be handled in a well-ventilated area, and contact with skin and eyes should be avoided. In case of exposure, affected areas should be rinsed thoroughly with water. As with all research chemicals, it should be handled with care and used only in accordance with safety guidelines.

According to an independent committee of scientific and health experts, ammoniazoline may be carcinogenic. Ammoniazoline is an odorless white crystal or white powder with a bitter taste. It has a melting point of 147-159℃ and does not decompose or sublimate under reduced pressure. It is used as a post-emergence herbicide. Ammoniazoline belongs to the triazole class of compounds, specifically 1H-1,2,4-triazole with an amino group substituted at the 3-position. It is used to control annual grasses and aquatic weeds (but not food crops because it causes cancer in laboratory animals). The EU banned the use of ammoniazoline in September 2017 due to its potential to pollute groundwater and pose risks to aquatic life; in addition, there are concerns about its endocrine-disrupting properties. Ammoniazoline acts as a herbicide, an EC 1.11.1.6 (catalase) inhibitor, and a carotenoid biosynthesis inhibitor. It is an aromatic amine belonging to the triazole class of compounds. Ammoniazoline is a colorless, odorless, crystalline aromatic amine with a bitter taste. Ammonium chloride is a widely used herbicide in non-food farmland for controlling annual and perennial grasses, pondweed, and broadleaf weeds. It has very low acute toxicity to humans, primarily manifesting as rash, diarrhea, nausea, vomiting, and nosebleeds. Ammonium chloride is a probable human carcinogen. (NCI05)
It is a non-selective post-emergence systemic herbicide. According to the Seventh Annual Report on Carcinogens (PB95-109781, 1994), it is a probable carcinogen. (Excerpt from Merck Index, 12th edition) It is an irreversible catalase inhibitor, thus impairing peroxisome activity.

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Mechanism of Action
Aztreon inhibits peroxisome activity in the liver and thyroid gland. Its mechanism of action in inducing thyroid tumors appears to be related to its goitrogenic effect, leading to elevated thyroid-stimulating hormone (TSH) levels… This study demonstrates that 3-amino-1,2,4-triazole is a potent inhibitor of glutathione peroxidase activity in erythrocytes. Furthermore, 3-amino-1,2,4-triazole inhibits arachidonic acid-induced malondialdehyde production in platelet-rich plasma and prostacyclin-like activity in the aortic rings. These results provide new evidence for the link between glutathione peroxidase activity and prostaglandin synthesis in rat platelets and arterial walls. This paper describes a technique for the cytochemical detection of peroxidase activity in unfixed guinea pig thyroid tissue. Both 3-amino-1,2,4-triazole and methimazole inhibited peroxidase activity in follicular cells (enzyme activity was still observed in erythrocytes), with maximum inhibition occurring at a concentration of 10 mmol. Interference with histidine metabolism, inhibition of pigment biosynthesis, or both, is considered the primary site of action for 3-amino-1,2,4-triazole (aminozazole). Arabidopsis thaliana is sensitive to 1,2,4-triazol-3-alanine, a feedback inhibitor of histidine biosynthesis, and histidine can reverse this effect. However, the combination of triazol-alanine and histidine did not reverse the medicinal effects of aztreol. This indicates that the toxicity of aztreol is not caused by histidine deficiency or by the accumulation of toxic intermediates in the histidine pathway. The concentration at which aztreol inhibits root elongation is lower than the concentration at which it causes leaf pigment depigmentation. Conversely, fluridone (a known inhibitor of carotenoid biosynthesis) does not inhibit root elongation. Fluridone also inhibits the accumulation of carotenoids in etiolated seedlings under dark conditions, but aztreol does not have this effect. Finally, gabakurin and axiflufen (but not aztreol) were able to prevent chlorophyll accumulation in Arabidopsis seedlings. ...
For more complete data on the mechanisms of action of aztreol (8 in total), please visit the HSDB record page.

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1H-1,2,4-Triazol-3-amine is a research chemical and herbicide, not an approved drug. It has no clinical trial or marketing approval status for therapeutic use. The compound is a small molecule irreversible inhibitor of catalase. It is used as a starting material for the synthesis of pharmaceutical compounds, such as antifungals, anticancer drugs, and inhibitors of enzymes associated with cardiovascular disease. In agrochemicals, it is used as a herbicide. The compound blocks the formation of 18S Fraction I protein, chloroplast DNA, and 70S ribosomes, and inhibits riboflavin biogenesis. It is a biochemical assay reagent featuring a triazole ring and an amino group at carbon 3. It should be stored in a cool, dry place.

C2H4N4

84.08

84.043

61-82-5

1639

Transparent to off white crystalline powder

1.8±0.1 g/cm3

85.4±23.0 °C at 760 mmHg

318 °F (NTP, 1992) ; 159 °C ; MP: 150-153 °C. /TECHNICAL GRADE/ ; MP: 153-159 °C. /TECHNICAL GRADE/ ; 159 °C ; 318 °F ; 152 °C ; 318 °F

5.4±22.6 °C

69.5±0.2 mmHg at 25°C

1.823

-1.67

2

3

0

6

44.8

0

C1=NC(=N)NN1

KLSJWNVTNUYHDU-UHFFFAOYSA-N

InChI=1S/C2H4N4/c3-2-4-1-5-6-2/h1H,(H3,3,4,5,6)

1H-1,2,4-triazol-5-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 100 mg/mL (1189.34 mM)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)