phenoloxidase[1]

Absorption, Distribution and Excretion
The compound is extensively metabolized in rabbits, with 86% excreted in urine within 2 days and another 10% in feces. The molecule undergoes extensive desulfurization, and the excretion of sulfur-labeled compounds is relatively slow. Ultimately, 60% is recovered as urinary sulfate. In rats and rabbits, the excretion rate of (35)-sulfur was slower after administration of (35)-sulfur compounds than after administration of (14)-carbon compounds. The results indicate that 1-phenyl-2-thiourea undergoes desulfurization in vivo, suggesting the release of some hydrogen sulfide, which may be the cause of its toxicity. Two hours after intraperitoneal injection of (35)-sulfur compounds in rats, the levels of (35)-sulfur were high in biotransformation and excretion organs (liver and kidneys) and in the lungs and thyroid gland affected by 1-phenyl-2-thiourea. Metabolites in rabbits include aniline, p-hydroxyphenylthiourea, phenylcyanamide, and phenylurea. (From the table) The S-oxidation of N-substituted thiourea by purified porcine liver mixed-function amine oxidase and porcine and hamster liver microsomal fractions was investigated. In the presence of the enzyme, oxygen, and nicotinamide adenine dinucleotide phosphate reductase, phenylthiourea was metabolized to the corresponding memidazine sulfinic acid… This reaction… proceeded via an intermediate sulfinic acid, indicating that two consecutive oxidation reactions occurred. The memidazine sulfinic acid product was then slowly autoxidized to the corresponding sulfonic acid.

Toxicity Summary
Identification and Uses: 1-Phenylacetyl-2-thiourea is a needle-like or prismatic solid substance with a bitter or tasteless taste (depending on individual genetic background). It is used in medical genetics research, as a repellent for rats, rabbits, and weasels, and in the production of rodenticides. Human Exposure and Toxicity: 1-Phenylacetyl-2-thiourea can be absorbed via ingestion and parenteral routes; it may also be absorbed and cause systemic toxicity after inhalation or skin contact. Bitterness perception (related to the ability to taste 1-phenyl-2-thiourea) is mediated by the tas2r38 gene. Some studies have found a higher proportion of taste loss in individuals with a family history of alcoholism than in controls, while other studies have not found this difference. Animal Experiments: Vomiting, coarse or labored breathing, cyanosis, and hypothermia may occur. Pleural effusion and pulmonary edema have been observed in experimental animals exposed to this compound, and the compound can destroy cytochrome P450 in vivo. Rats injected with 1-phenyl-2-thiourea experienced hypoglycemia lasting up to 5 hours. In mice, this compound was almost as effective as high-dose potassium iodide in reducing sucrose intake. 1-Phenylacetyl-2-thiourea produced a concentration-dependent inhibition of acetylcholinesterase activity in rat lungs in vitro. Phenylacetyl-2-thiourea induced mutagenicity in a Salmonella typhimurium mutagenesis assay without S9 activation, but was negative in a Salmonella/microsomal pre-incubation assay. At a standard concentration of 0.003% (200 μM), 1-Phenylacetyl-2-thiourea inhibited melanin production, with minimal reported other effects on zebrafish embryonic development. Administration of 0.003% 1-Phenylacetyl-2-thiourea altered the regulation of neural crest and mesodermal components (craniofacial development) by retinoic acid and insulin-like growth factor. Although the morphology of the control group treated with 1-Phenylacetyl-2-thiourea was normal, 1-Phenylacetyl-2-thiourea still reduced the teratogenic effects of retinoic acid on the pharyngeal arch and jaw cartilage. 1-Phenylacetyl-2-thiourea inhibited neural crest development at higher concentrations (0.03%), with the strongest inhibitory effect observed when added before 22 hours post-fertilization (hpf). Addition of 0.003% 1-phenyl-2-thiourea during 4 to 20 hours post-fertilization (hpf) reduced thyroxine (T4) levels in the nasopharyngeal thyroid follicles of 96 hpf embryos. 1-Phenylacetyl-2-thiourea is an experimental teratogen in mice. In a 78-week NTP feeding study, 1-phenyl-2-thiourea was not carcinogenic in male and female rats (120 and 60 ppm) and mice (300 and 150 ppm).

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Interactions
This study investigated the combined effects of dopamine and 1-methyl-4-phenylpyridinium (MPP(+)) on isolated brain mitochondrial membrane permeability and PC12 cell viability.
MPP(+) enhanced the inhibitory effects of dopamine on mitochondrial swelling, membrane potential, and Ca²⁺ transport, and this effect was not inhibited by antioxidant enzymes (SOD and catalase). Both dopamine and MPP(+) led to decreased transmembrane potential, increased reactive oxygen species (ROS), glutathione (GSH) depletion, and cell death in PC12 cells. Antioxidant enzymes mitigated these effects of dopamine and MPP(+) on PC12 cells. The combined effects of dopamine and MPP(+) resulted in decreased transmembrane potential and increased ROS generation in PC12 cells, exhibiting an additive effect. The dopamine-MPP(+) combined effect induced GSH depletion and cell death in PC12 cells, which were not inhibited by antioxidant enzymes, rutin, diethylstilbestrol, or ascorbic acid. Melanin led to decreased PC12 cell viability. N-acetylcysteine, N-phenylthiourea, and 5-hydroxyindole reduced cell death induced by co-addition of dopamine and MPP(+) and the formation of dopaquinone and melanin, while depranilide and clogilis did not show inhibitory effects. The results indicate that co-addition of dopamine with MPP(+) enhances altered mitochondrial membrane permeability and cell death, likely due to the toxic quinones and melanin produced by MPP(+)-stimulated dopamine oxidation. Pretreatment of animals with 1-methyl-1-phenylthiourea prevents desulfurization and reduces PTU toxicity. Cysteine and reduced glutathione partially reduce the glycogen depletion effect of toxic doses of phenylthiourea on rat liver. The presence of phenylthiourea antagonizes the in vitro binding of (14)-carbazide to rat lung proteins. For more complete data on interactions of 1-phenyl-2-thiourea (7 in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats: 3 mg/kg
Oral LD50 in rabbits: 40 mg/kg
Intraperitoneal LD50 in rats: 5 mg/kg
Oral LD50 in mice: 10 mg/kg
Intraperitoneal LD50 in mice: 25 mg/kg

[1]. The phenylthiourea is a competitive inhibitor of the enzymatic oxidation of DOPA by phenoloxidase. J Enzyme Inhib Med Chem. 2012 Feb;27(1):78-83.

Needle-shaped crystals. Used in the manufacture of rodenticides and medical genetics. (EPA, 1998)
N-Phenylethiourea is a type of thiourea compound in which one hydrogen atom is replaced by a phenyl group. Depending on genetic makeup, human perception of its taste varies greatly; some find it very bitter, while others find it tasteless. This unique property led to N-phenylthiourea being used for paternity testing before the advent of DNA testing technology. It is an EC 1.14.18.1 (tyrosinase) inhibitor. Its function is similar to that of thiourea.
Phenylethiourea is a thiourea derivative containing a benzene ring. Depending on genetic makeup, humans may perceive it as bitter or tasteless.
Mechanism of Action

Thyroid hormone (T4) can be detected in thyroid follicles three days after the thyroid gland has differentiated. Conversely, embryos or larvae treated with goitrogenic substances (such as methimazole, potassium perchlorate, and 6-n-propyl-2-thioureapyrimidine) lack thyroid hormone immunoreactivity. Phenylephrine (PTurea; also commonly known as PTU) is widely used in zebrafish research to inhibit pigmentation in developing embryos/fry. PTUrea contains a thiourea group, which is the source of the goitrogenic activity of methimazole and 6-n-propyl-2-thioureapyrimidine. This study shows that a commonly used dose of 0.003% phenylthiourea eliminates T4 immunoreactivity in the thyroid follicles of zebrafish larvae. Since thyroid development is unaffected, these data suggest that phenylthiourea inhibits the production of thyroid hormones. Like other goitrogenic substances, phenylthiourea causes delayed hatching, developmental delays, and malformations in embryos or larvae, and the symptoms worsen with increasing doses. However, at a dose of 0.003% phenylthiourea, the toxic side effects appear to be minimal, and maternally supplied thyroid hormones may compensate for impaired thyroid function in early development. The ability to taste phenylthiourea (PTC) is a classic human genetic trait and has been the subject of genetic and anthropological research for over 70 years. This trait is also associated with various dietary preferences and may therefore have significant implications for human health. Recent identification of the gene responsible for this phenotype has yielded some surprising findings. This gene belongs to the T2R bitter taste receptor gene family. It exists in seven different allelic forms, but only two—a predominantly taste-sensitive type and a predominantly taste-insensitive type—are predominantly non-taste-sensitive outside of sub-Saharan Africa. The non-taste-sensitive allele is located in a small, highly homologous chromosomal region, suggesting that non-taste-sensitive individuals originated from an ancient ancestral individual, consistent with the view that the origin of the non-taste-sensitive allele predates the migration of modern humans out of Africa. The two predominant forms differ at three amino acid sites, and both alleles are maintained at a high frequency through balanced natural selection, suggesting that the non-taste-sensitive allele has some function. We hypothesize that this function is as a receptor for another yet-to-be-identified toxic bitter substance. At least some of the remaining five haplotypes appear to confer moderate sensitivity to phenylthiourea (PTC), suggesting that further research is needed into the relationship between receptor structure and taste function. Human bitter taste perception is mediated by the hTAS2R subfamily of G protein-coupled membrane receptors (GPCRs). Currently, structural information about these receptors is limited. This paper utilizes structural bioinformatics and molecular docking methods to identify residues in one of the most extensively studied hTAS2Rs (hTAS2R38) involved in phenylthiourea (PTC) binding and receptor activation. The predicted results were validated by site-directed mutagenesis experiments involving specific residues located at the putative binding site and transmembrane (TM) helices 6 and 7 (potentially involved in receptor activation). Based on our measurements, we conclude that: (i) residue N103 actively participates in PTC binding, consistent with previous computational studies; (ii) W99, M100, and S259 collectively determine the size and shape of the binding cavity; and (iii) W99 and M100, along with F255 and V296, play crucial roles in receptor activation, providing insights previously unrevealed in computational models of bitter taste receptor activation.

C7H8N2S

152.22

152.04

103-85-5

676454

Needles from water; prisms from alcohol
Needles

1.3±0.1 g/cm3

266.7±23.0 °C at 760 mmHg

145-150 °C(lit.)

115.1±22.6 °C

0.0±0.5 mmHg at 25°C

1.725

0.73

2

1

1

10

119

0

FULZLIGZKMKICU-UHFFFAOYSA-N

InChI=1S/C7H8N2S/c8-7(10)9-6-4-2-1-3-5-6/h1-5H,(H3,8,9,10)

phenylthiourea

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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 (656.94 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (16.42 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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 (16.42 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.

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