phenoloxidase[1]

Absorption, Distribution and Excretion
Extensively metabolized in rabbits & 86% excreted in urine over 2 days with addnl 10% in feces. Desulfuration of the molecule is extensive, & the sulfur label is excreted more slowly. Eventually 60% is recovered as urinary sulfate.
After admin of (35)Sulfur-cmpd to ... /rats & rabbits/ excretion of (35)Sulfur was slower compared to that of (14)Carbon after (14)Carbon-cmpd. ... /Results/ indicated that desulfuration of 1-phenyl-2-thiourea occurred in vivo & ... suggested that some hydrogen sulfide was liberated ... & may be responsible for toxic effects ... 2 hr after ip admin of (35)Sulfur-cmpd to rats, levels of (35)Sulfur were high in organs of biotransformation & excretion (liver & kidneys) & also in lung & thyroid gland, organs affected by 1-phenyl-2-thiourea.

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Metabolism / Metabolites
Yields aniline, p-hydroxyphenylthiourea, phenylcyanamide, & phenylurea in rabbit. /From table/
... Investigated S-oxidation of N-substituted thioureas by purified hog liver mixed-function amine oxidase and pig and hamster liver microsomal fractions. In the presence of enzyme, O2, and nicotinamide adenine dinucleotide phosphate reductase, phenylthiourea ... metabolized to the corresponding formamidine sulfinic acid ... reaction ... occurred through intermediary sulfenic acids, indicating two consecutive oxidations. The formamidine sulfinic acid products then auto-oxidized slowly to the corresponding sulfonic acids.

Toxicity Summary
IDENTIFICATION AND USE: 1-Phenyl-2-thiourea is a bitter or tasteless (depending on the individual's genetic background) needle- or prism-like solid material used in medical genetics studies, as a repellent for rats, rabbits, and weasels, and in the production of rodenticides. HUMAN EXPOSURE AND TOXICITY: 1-Phenyl-2-thiourea can be absorbed by ingestion and parenterally; it may be absorbed and cause systemic toxicity following inhalation or dermal exposure. The bitter taste perception (associated with the ability or inability to taste 1-phenyl-2-thiourea) is mediated by the tas2r38 gene. Some studies have found higher proportions of nontasters among those with a family history of alcoholism than controls, whereas others have not. ANIMAL STUDIES: Vomiting, noisy or difficult breathing, cyanosis, and hypothermia may occur. Pleural effusions and pulmonary edema have been seen in exposed experimental animals, and this compound destroys cytochrome P450 in vivo. Hypoglycemia lasting for up to 5 hours was seen in rats injected with 1-phenyl-2-thiourea. In mice it was nearly as effective as a strong dose of licl in reducing sucrose drinking. 1-Phenyl-2-thiourea produced a concn-dependent inhibition of rat lung acetylcholinesterase activity in vitro. Phenylthiourea caused mutagenicity in the Salmonella typhimurium assay without S9 activation, but was negative in the salmonella/microsome preincubation assay. At the standard concentration of 0.003% (200 uM), 1-phenyl-2-thiourea inhibits melanogenesis and reportedly has minimal other effects on zebrafish embryogenesis. The administration of 0.003% 1-phenyl-2-thiourea altered retinoic acid and insulin-like growth factor regulation of neural crest and mesodermal components of craniofacial development. 1-Phenyl-2-thiourea also decreased retinoic acid-induced teratogenic effects on pharyngeal arch and jaw cartilage despite morphologically normal appearing 1-phenyl-2-thiourea -treated controls. 1-Phenyl-2-thiourea inhibited neural crest development at higher concentrations (0.03%) and had the greatest inhibitory effect when added prior to 22 hours post fertilization (hpf). Addition of 0.003% 1-phenyl-2-thiourea between 4 and 20 hpf decreased thyroxine (T4) in thyroid follicles in the nasopharynx of 96 hpf embryos. 1-Phenyl-2-thiourea is an experimental teratogen in mice. In NTP 78 weeks feeding study 1-phenyl-2-thiourea was not carcinogenic to rats (120 and 60 ppm) and mice (300 and 150 ppm) in both males or females.

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Interactions
The present study examined the combined effect of dopamine and 1-methyl-4-phenylpyridinium (MPP(+)) on the membrane permeability in isolated brain mitochondria and on cell viability in PC12 cells. MPP(+) increased effect of dopamine against the swelling, membrane potential, and Ca(2+) transport in isolated mitochondria, which was not inhibited by the addition of antioxidant enzymes (SOD and catalase). Dopamine or MPP(+) caused the decrease in transmembrane potential, increase in reactive oxygen species, depletion of GSH, and cell death in PC12 cells. Antioxidant enzymes reduced each effect of dopamine and MPP(+) against PC12 cells. Co-addition of dopamine and MPP(+) caused the decrease in the transmembrane potential and increase in the formation of reactive oxygen species in PC12 cells, in which they showed an additive effect. Dopamine plus MPP(+)-induced the depletion of GSH and cell death in PC12 cells were not decreased by the addition of antioxidant enzymes, rutin, diethylstilbestrol, and ascorbate. Melanin caused a cell viability loss in PC12 cells. The N-acetylcysteine, N-phenylthiourea, and 5-hydroxyindole decreased the cell death and the formation of dopamine quinone and melanin induced by co-addition of dopamine and MPP(+), whereas deprenyl and chlorgyline did not show an inhibitory effect. The results suggest that co-addition of dopamine and MPP(+) shows an enhancing effect on the change in mitochondrial membrane permeability and cell death, which may be accomplished by toxic quinone and melanin derived from the MPP(+)-stimulated dopamine oxidation.
Pretreatment of animals with 1-methyl-1-phenylthiourea prevents desulfuration & reduces toxicity of PTU.
Cysteine & reduced glutathione partially reduced the liver glycogen-depleting effect of a toxic phenylthiourea dose in rats.
In vitro binding of (14)Carbon thiourea to rat lung protein was antagonized by the presence of phenylthiourea.
For more Interactions (Complete) data for 1-PHENYL-2-THIOUREA (7 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 3 mg/kg
LD50 Rabbit oral 40 mg/kg
LD50 Rat ip 5 mg/kg
LD50 Mouse oral 10 mg/kg
LD50 Mouse ip 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-like crystals. Used in the manufacture of rodenticides and in medical genetics. (EPA, 1998)
N-phenylthiourea is a member of the class of thioureas that is thiourea in which one of the hydrogens is replaced by a phenyl group. Depending on their genetic makeup, humans find it either very bitter-tasting or tasteless. This unusual property resulted in N-phenylthiourea being used in paternity testing prior to the advent of DNA testing. It has a role as an EC 1.14.18.1 (tyrosinase) inhibitor. It is functionally related to a thiourea.
Phenylthiourea is a THIOUREA derivative containing a phenyl ring. Depending on their genetic makeup, humans can find it either bitter-tasting or tasteless.

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Mechanism of Action
Thyroid hormone (T4) can be detected in thyroid follicles in wild-type zebrafish larvae from 3 days of development, when the thyroid has differentiated. In contrast, embryos or larvae treated with goitrogens (substances such as methimazole, potassium percholorate, and 6-n-propyl-2-thiouracil) are devoid of thyroid hormone immunoreactivity. Phenythiourea (PTurea; also commonly known as PTU) is widely used in zebrafish research to suppress pigmentation in developing embryos/fry. PTurea contains a thiocarbamide group that is responsible for goitrogenic activity in methimazole and 6-n-propyl-2-thiouracil. In the present study, /this research/ shows that commonly used doses of 0.003% PTurea abolish T4 immunoreactivity of the thyroid follicles of zebrafish larvae. As development of the thyroid gland is not affected, these data suggest that PTurea blocks thyroid hormone production. Like other goitrogens, PTurea causes delayed hatching, retardation and malformation of embryos or larvae with increasing doses. At doses of 0.003% PTurea, however, toxic side effects seem to be at a minimum, and the maternal contribution of the hormone might compensate for compromised thyroid function during the first days of development.
The ability or inability to taste the compound phenylthiocarbamide (PTC) is a classic inherited trait in humans and has been the subject of genetic and anthropological studies for over 70 years. This trait has also been shown to correlate with a number of dietary preferences and thus may have important implications for human health. The recent identification of the gene that underlies this phenotype has produced several surprising findings. This gene is a member of the T2R family of bitter taste receptor genes. It exists in seven different allelic forms, although only two of these, designated the major taster and major non-taster forms, exist at high frequency outside sub-Saharan Africa. The non-taster allele resides on a small chromosomal region identical by descent, indicating that non-tasters are descended from an ancient founder individual, and consistent with an origin of the non-taster allele preceding the emergence of modern humans out of Africa. The two major forms differ from each other at three amino acid positions, and both alleles have been maintained at high frequency by balancing natural selection, suggesting that the non-taster allele serves some function. We hypothesize that this function is to serve as a receptor for another, as yet unidentified toxic bitter substance. At least some of the remaining five haplotypes appear to confer intermediate sensitivity to PTC, suggesting future detailed studies of the relationships between receptor structure and taste function.
Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models.

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.)