IL-17 mRNA is strongly inhibited by Enilconodium sulfate (Enilconodium; 3, 10, 30 μM; 6 hours duration)[1]. RT-PCR of sulfate expression exclusively in mPXR using imazalil (1, 3, 10, 30, 100 μM) over 24 hours [1].

Imazalil (enconazole; 25-100 mg/kg; intraperitoneal) sulfate dramatically raises cardiac Cyp3a11 mRNA levels in a dosed manner [2]. Imazalil (75 mg/kg; i.p.; twice; one daily) sulfate coupled with TCPOBOP (3 mg/kg) significantly raised the number of Ki-67 positive nuclei and Mcm2 mRNA compared with treatment alone level. Imazalil sulfate can increase TCPOBOP treatment-mediated liver cell proliferation [2]. (0.1, 0.5, 2.5 mg/kg; in floods; for 15 weeks) Sulfate induces oxidation termination and bile acid action in camels C57BL/6 camels [3].

RT-PCR[1]
Cell Types: EL4 cells
Tested Concentrations: 3, 10, 30 μM
Incubation Duration: 6 h
Experimental Results: Significant inhibition of IL-17 mRNA. Reporter gene expression is induced dose-dependently in HepG2 cells [2].

Animal/Disease Models: IMZ Male C57BL/6N mice [2]
Doses: 25, 50, 75, 100 mg/kg
Route of Administration: intraperitoneal (ip) injection; single dose
Experimental Results: Dramatically increased liver Cyp3a11 mRNA levels in a dose-dependent manner.

Absorption, Distribution and Excretion
A comparison of excretion patterns after oral and intravenous administration showed that oral administration of mizoribine resulted in higher bioavailability (and therefore absorption). Four groups of Wistar rats were administered mizoribine technical grade (purity = 98.7%) and ¹⁴C-imizoribine (117.1 uCi/mL; purity = 99.9%), with 6-8 rats in each group. Group A: 5 rats per sex, with a reserve group of 1 rat per sex, received a single dose of ¹⁴C-imizoribine via tail vein injection. Group B: 5 rats per sex received a single dose of ¹⁴C-imizoribine via gastric tube instillation. Group C: 5 rats per sex, with a reserve group K (3 rats per sex) receiving 1.25 mg/kg/day of mizoribine via gastric tube instillation for 14 consecutive days. Twenty-four hours after the last unlabeled dose, five rats of each sex were given a single oral dose of 1.25 mg/kg of 14C-imizolid. Group D (n=5 of each sex) and the reserve group L (n=1 of each sex) received a single intragastric infusion of 20 mg/kg of 14C-imizolid. Ninety-six hours post-administration, rats in groups B, C, and D were sacrificed and tissues collected. Group A and the reserve rats (unused rats) were sacrificed and discarded. Distribution results showed that only 1% of 14C-imizolid was recovered from tissues and cadavers after 96 hours. Compound levels in tissues were dose-responsive, but no accumulation was observed after multiple administrations. No sex differences were found. Ninety-six hours after gavage, approximately 50% of the tissue-specific 14C-imidazole was recovered in the liver, with concentrations approximately 20 times higher than the corresponding blood concentrations. Concentrations in the kidneys, lungs, and adrenal glands were approximately 4–10 times higher than the corresponding blood concentrations. Concentrations of 14C-imidazole in all other tested tissues were lower than in blood, and it was not detected in brain tissue. Most (approximately 90%) of the radioactive material was eliminated from the body within 24 hours via all routes and methods of administration (primarily through urine, with slightly higher levels in females). The effectiveness of thiabendazole (TBZ), benomyl, imidazolid, and propiconazole in controlling Penicillium and Green mold was significantly reduced due to the delayed treatment time. While imidazolid and propiconazole exhibited lower protective activity, they showed higher efficiency against sporulation. On the other hand, thiabendazole and benomyl could protect the fruit from subsequent infection. Studies found that storage significantly affected the residual activity of imidazolid compared to thiabendazole. Residues of imidazolid and thiabendazole were detected in orange marmalade made from fruit treated with fungicides. Imidazolid is rapidly absorbed, distributed, and metabolized in rodents. It is a sulfate, with approximately 90% excreted within 96 hours. Metabolites/Metabolites… In rats, very little imidazolid is excreted unchanged: less than 1% of the administered dose is found in feces, and only trace amounts in urine. The compound is metabolized into at least 25 metabolites. Three major metabolites were identified: (+/-)-1-[2-(2,4-dichlorophenyl)-2-(2,3-dihydroxypropoxy)ethyl]-imidazolidine-2,5-dione (metabolite 8), (+/-)-1-[2-(2,4-dichlorophenyl)-2-(2,3-dihydroxypropoxy)ethyl]-1H-imidazolium (metabolite 10), and (+/-)-1-(2,4-dichlorophenyl)-2-imidazolium-1-ylethanol (metabolite 11). The main metabolic pathways included epoxidation, epoxide hydration, oxidative O-dealkylation, oxidation and cleavage, and oxidative N-dealkylation. The metabolic patterns were similar after oral and intravenous administration and in animals of different sexes.
Biological half-life
In humans, the half-life is approximately 2 hours.

Toxicity Data
LC50 (Rat) = 16,000 mg/m³/4h

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640 mg/kg LC50 (Rats, Inhalation) 16 g/m³/4 hr LD50 (Rats, Dermal) 4200 mg/kg LD50 (Rats, Intraperitoneal) 155 mg/kg

[1]. Hiroyuki Kojima, et al. Inhibitory effects of azole-type fungicides on interleukin-17 gene expression via retinoic acid receptor-related orphan receptors α and γ. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):338-45.
[2]. Shohei Yoshimaru, et al. Acceleration of murine hepatocyte proliferation by imazalil through the activation of nuclear receptor PXR. J Toxicol Sci. 2018;43(7):443-450.
[3]. Cuiyuan Jin, et al. Chronic exposure of mice to low doses of imazalil induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels. Environ Toxicol. 2018 Jun;33(6):650-658.

Imidazolidinone is a slightly yellow to brown, solidified oily substance that is non-corrosive and used as a fungicide. Mechanism of Action Two single-copy genes, named atrA and atrB (ATP-binding cassette transporters A and B), were cloned and sequenced from the filamentous fungus Aspergillus nidus. Based on the presence of conserved motifs and hydrophobicity analysis, the products encoded by atrA and atrB can be considered new members of the ATP-binding cassette (ABC) superfamily of membrane transporters. These two products share the same topological structure as the ABC transporters PDR5 and SNQ2 of Saccharomyces cerevisiae and CDR1 of Candida albicans, which are involved in multidrug resistance in these yeasts. The ATP-binding cassettes of atrA and atrB also show significant homology with the ATP-binding cassettes of mammalian ABC transporters (P-glycoproteins). In A. nidulans mycelium, transcription of atrA and atrB was significantly enhanced after treatment with a variety of agents, including antibiotics, azole fungicides, and phytotoxicants. This enhanced transcription was detected within minutes of treatment, consistent with previously reported onset of energy-dependent efflux activity against azole fungicides in this fungus. Researchers investigated atr gene transcription in wild-type strains and a series of homologous strains carrying the imaA and/or imaB genes, which confer multidrug resistance to a variety of toxic compounds, such as the azole fungicide imidazolid. Constitutive transcriptional levels of atrB were low in both wild-type and strains carrying either the imaA or imaB genes. Imidazolidone treatment enhanced atrB transcription to a similar degree in all tested strains. Unlike atrB, atrA exhibited relatively high constitutive expression levels in mutants carrying imaB. Imidazolidin showed a stronger enhancing effect on atrA transcription in the imaB mutant, indicating that the imaB locus regulates atrA. Functional analysis showed that the atrB cDNA can compensate for drug hypersensitivity associated with DPR5 deficiency in Saccharomyces cerevisiae.

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Therapeutic Use
MeSH Title: Industrial Fungicides
Veterinary Drugs: Antifungal Drugs
... Used to treat human Alternaria alternata infection, a rare infection.

C14H16CL2N2O5S

395.26

360.01

58594-72-2

Imazalil-d5 sulfate;1398065-92-3

173636

Slightly yellow to brown crystalline mass.
Solidified oil
Brownish oil

1.23g/cm3

448.5ºC at 760mmHg

52.7ºC

225.1ºC

4.561

2

6

6

24

372

0

C=CCOC(CN1C=CN=C1)C2=C(C=C(C=C2)Cl)Cl.OS(=O)(=O)O

XVTXMTOYQVRHSK-UHFFFAOYSA-N

InChI=1S/C14H14Cl2N2O.H2O4S/c1-2-7-19-14(9-18-6-5-17-10-18)12-4-3-11(15)8-13(12)16;1-5(2,3)4/h2-6,8,10,14H,1,7,9H2;(H2,1,2,3,4)

1-[2-(2,4-dichlorophenyl)-2-prop-2-enoxyethyl]imidazole;sulfuric acid

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)

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.)