Hexazinone targets photosystem II (PSII) in plants, inhibiting the photosynthetic electron transport chain. By binding to the D1 protein of the PSII reaction center, it blocks the transfer of electrons from plastoquinone, thereby inhibiting the light-dependent reactions of photosynthesis. This mechanism is classified as HRAC Group C2 and WSSA Group 5. As a herbicide, it does not have a classical molecular target in mammals.

Hexazinone is not used in pharmacological activity assays. Its activity is assessed in plant-based bioassays that measure its ability to inhibit photosynthesis and plant growth. The inhibition of photosynthetic electron transport can be measured by monitoring chlorophyll fluorescence or oxygen evolution in isolated chloroplasts or intact plant tissues. It has a broad spectrum of activity against weeds and woody plants.

Hexazinone is effective in vivo as a herbicide for the control of weeds and woody plants. It is applied to soil or foliage and is absorbed by plants, where it inhibits photosynthesis and leads to plant death. It is used in forestry for site preparation and in agriculture for weed control in various crops.

Hexazinone does not have a conventional enzyme/receptor binding assay in the context of mammalian pharmacology. Its activity is assessed in plant-based assays. The inhibition of photosynthetic electron transport can be measured using isolated chloroplasts or thylakoid membranes, where the compound's ability to inhibit the reduction of DCPIP or other electron acceptors is measured.

Hexazinone is not typically used in cell-based assays for pharmacological purposes. Its effects are studied in plant systems. The compound's effects on plant cell cultures can be assessed by measuring photosynthetic activity, cell growth, and viability. However, its primary applications are in agriculture rather than cellular research.

In vivo animal experiments for Hexazinone are not typical for pharmacological purposes. It is used in agricultural settings for weed control. Toxicological studies in animals have been conducted to assess its safety. However, these are toxicological rather than pharmacological studies.

Absorption, Distribution and Excretion
Oral administration of hexaazine has not been shown to preferentially accumulate in any tissue. /Dosage not specified/ …Hexaazine was added to dairy cow feed at 0, 1, 5 or 25 ppm for 30 days. …No residues were detected in milk, fat, liver, kidney or lean meat. …The treatment methods for three groups of male and female Sprague Dawley rats were as follows: (1) Group A received a single low dose of (14)C-hexaazine (14 mg/kg) by gavage without pretreatment (treated with non-radioactive hexaazine); (2) Group B received a single low dose of (14)C-hexaazine (14 mg/kg) by gavage after three weeks of pretreatment with 100 ppm non-radioactive hexaazine; (3) Group C rats received a single high dose of (14)C-hexaazine (1000 mg/kg) by gavage without pretreatment. Hexazinone is rapidly metabolized via hydroxylation and demethylation and excreted in urine and feces over a test period of 3 to 6 days. Approximately 77% and 20% (dose) of (14)C-hexazinone were excreted in urine and feces, respectively. Almost all radioactive material was recovered within 24 hours of administration. Very low levels of radioactive material (approximately 0.2% of the dose) were detected in the gastrointestinal tract, skin, organs (heart, lungs, liver, spleen, kidneys, brain, and testes or ovaries), muscle, fat, and blood. Male rats were fed 2500 ppm (125 mg/kg) hexazinone in their diet for 17 days. Subsequently, the subjects received a single injection of 18.3 mg/300 g (61 mg/kg) of (14)C-labeled hexazinone. Hexazinone was rapidly absorbed within 72 hours, with 61% detected in urine and 32% in feces. Trace amounts were detected in the gastrointestinal tract (0.6%, tissue not specified) and exhaled air (0.08%). For more complete data on the absorption, distribution, and excretion of hexazinones (8 in total), please visit the HSDB record page. The major metabolites of hexazinones in rat urine include: 3-(4-hydroxycyclohexyl)-6-(dimethylamino)-1-methyl-1,3,5-triazin-2,4-(1H,3H)-dione (metabolite A); 3-cyclohexyl-6-(methylamino)-1-methyl-1,3,5-triazin-2,4-(1H,3H)-dione (metabolite B); and 3-(4-hydroxycyclohexyl)-6-(methylamino)-1-methyl-1,3,5-triazin-2,4-(1H,3H)-dione (metabolite C). The detection rates of these metabolites in urine were 46.8%, 11.5%, and 39.3%, respectively. The main metabolites in feces were A (26.3%) and C (55.2%). The levels of hexaazinone, which was not detected in either urine or feces, were both below 1%.
Hexazinone has a molecular weight of 252.31 g/mol and a molecular formula of C12H20N4O2. Its IUPAC name is 3-cyclohexyl-6-(dimethylamino)-1-methyl-1,3,5-triazine-2,4-dione. It has a melting point of 97-100.5°C. It is soluble in chloroform and ethyl acetate.

Toxicity Summary
Identification and Uses: Hexazinone is a white crystalline solid used as a herbicide. Human Exposure and Toxicity: A 26-year-old female experienced vomiting within 24 hours after inhaling hexazinone dust. Animal Studies: In a 10-day study, male rabbits were percutaneously treated with hexazinone for 6 hours daily at doses of 70 or 680 mg/kg/day without any signs of skin irritation or toxicity. A trend toward increased serum alkaline phosphatase (SAP) and serum alanine aminotransferase (SGPT) activities was observed. Hexazinone caused severe eye irritation in rabbits. The only detectable difference was a slightly lower growth curve in rats fed 5000 ppm hexazinone compared to the control group. Extending the feeding period to 2 years resulted in weight loss in male rats fed 2500 ppm and female rats fed 1000 or 2500 ppm. All other response parameters, including tumor type and incidence, were similar between the experimental and control groups. After 8 weeks of administration at concentrations up to 10,000 ppm, only the highest concentration group of mice showed an increase in liver weight, with no other changes observed. Two years of administration at 200, 2500, or 10,000 ppm resulted in tail tip detachment, and mice administered 10,000 ppm showed an increase in liver weight. Mice administered 2500 or 10,000 ppm showed central lobular hepatocyte hypertrophy and an increase in proliferative nodules. No evidence of tumorigenicity was observed. Dogs administered 5000 ppm hexaazine for 90 consecutive days showed slower weight gain and clinical signs such as enzymatic changes suggestive of liver damage. However, microscopic examination of the liver revealed no abnormalities, and dogs administered 200 ppm or 1000 ppm showed no significant difference from the control group. No teratogenic effects were observed in rats and rabbits, and the reproductive capacity of rats administered up to 2500 ppm hexaazine for three generations was not affected. No carcinogenicity was detected in rat pups fed up to 5000 ppm hexaazinone for two years. Similarly, no increased tumor incidence was observed in mice fed up to 10000 ppm hexaazinone. At concentrations up to 7000 μg/plate, hexaazinone was negative for mutagenicity testing against Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98, and TA 100. Ecotoxicity studies: Two bird breeding studies showed that the no observed effect concentration (NOEC) in quail was < 100 ppm, while the NOEC in mallards was > 1000 ppm. Signal crayfish showed higher sensitivity to hexaazinone than fish and could serve as a biological indicator of environmental pollution. The ability of hexaazinone to control aquatic weeds was tested at a concentration of 1.0 ppm in a 0.08 hectare pond. Within 5 days post-treatment, dissolved oxygen decreased from 8.0 ppm to 0.2 ppm, which appears to be the cause of the fish mortality observed 4 days post-treatment.

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Non-human toxicity values
Oral LD50 in rats: 860 mg/kg
Oral LD50 in rats: 1690 mg/kg
Dermal LD50 in rats: 5278 mg/kg
Oral LD50 in guinea pigs: 860 mg/kg
For more complete non-human toxicity data on hexaquinones (9 in total), please visit the HSDB records page.
Hexazinone is a herbicide and is not intended for human use. Its toxicological profile has been evaluated for occupational exposure and environmental impact. It is considered to have low acute toxicity to mammals but may cause eye irritation. Its safety for use in agriculture has been established through regulatory review.

[1]. Hexazinone.From Wikipedia.

Hexazinone is a white crystalline solid, corrosive and irritating, used as a herbicide. Hexazinone belongs to the 1,3,5-triazine class of compounds. It is an organic compound used as a broad-spectrum herbicide. It is a colorless solid with some solubility in water, but high solubility in most organic solvents except alkanes. As a triazine herbicide, it is manufactured by DuPont under the trade name Velpar. Mechanism of Action: Inhibits photosynthesis in photosystem II.
Hexazinone is a broad-spectrum herbicide belonging to the triazine family. It inhibits photosynthesis by targeting photosystem II (PSII) in plants. It is used for weed control in forestry, agriculture, and industrial sites. The compound is available from various chemical suppliers for research purposes.

C12H20N4O2

252.3128

252.158

51235-04-2

Hexazinone-d6;1219804-22-4

39965

White to off-white solid powder

1.3±0.1 g/cm3

332.8±25.0 °C at 760 mmHg

97-100.5ºC

155.1±23.2 °C

0.0±0.7 mmHg at 25°C

1.612

1.85

0

2

2

18

386

0

O=C(N1C2CCCCC2)N(C)C(N(C)C)=NC1=O

CAWXEEYDBZRFPE-UHFFFAOYSA-N

InChI=1S/C12H20N4O2/c1-14(2)10-13-11(17)16(12(18)15(10)3)9-7-5-4-6-8-9/h9H,4-8H2,1-3H3

3-cyclohexyl-6-(dimethylamino)-1-methyl-1,3,5-triazine-2,4-dione

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 (~396.3 mM; with ultrasonication)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.91 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well.

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