| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
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| Targets |
Tienilic acid targets cytochrome P450 enzymes, specifically acting as a mechanism-based inhibitor (suicide substrate) of CYP2C9 and CYP2C10. The metabolic reaction carried out by these enzymes converts tienilic acid to a thiophene sulfoxide intermediate, which is highly electrophilic. This intermediate forms covalent bonds with the enzyme's active site, leading to irreversible inhibition.
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| ln Vitro |
In vitro, Tienilic acid is a specific suicide substrate for CYP2C9 and CYP2C10. It is converted by cytochrome P450 enzymes to reactive electrophilic metabolites. The compound inhibits CYP2C9 activity through mechanism-based inactivation. Tienilic acid is not detectable with CYP2C18 and CYP2C8. It also interacts with proteins involved in drug metabolism and uric acid excretion.
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| ln Vivo |
Tinic acid is found only in plasma, is eliminated through bile and fasting urine, and is found in various drugs that have slight variations. It is administered orally and intravenously in single doses (100 mg/lg in rats and mice, 5 mg/kg in pigs and dogs). creatures[2]. Tinic acid (0-480 mg/kg; oral; for 28 days) causes single-cell necrosis in small populations of hepatocytes and lowers blood pressure, serum, hemoglobin, uric acid, and S-GPT [3].
In vivo, Tienilic acid acts as a diuretic and antihypertensive agent with uricosuric activity. It was formerly marketed for the treatment of hypertension. The compound was withdrawn from the market because of hepatotoxicity. Tienilic acid is used as a model compound for studying the metabolism and toxicity of thiophene-containing drugs. |
| Enzyme Assay |
Tienilic acid's enzyme inhibition activity has been characterized using human yeast-expressed cytochromes P450 2C8, 2C9, 2C18, and 2C19. Enzyme assays typically involve incubating tienilic acid with CYP2C9 enzyme preparations and measuring the loss of enzymatic activity over time. The compound is a mechanism-based inhibitor specific of cytochrome P450 2C9.
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| Cell Assay |
In vitro cell experiments with Tienilic acid typically use hepatocytes or cell lines expressing CYP2C9 to study its metabolism and toxicity. Cells are treated with the compound, and the formation of reactive metabolites, covalent binding to proteins, and cellular toxicity are assessed. The compound's effects on drug metabolism and detoxification pathways are evaluated.
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| Animal Protocol |
Animal/Disease Models: Rats, mice, pigs and dogs [2]
Doses: rats and mice 100 mg/lg, pigs and dogs 5 mg/kg Route of Administration: oral and intravenous (iv) (iv)injection; single dose Experimental Results: plasma only Significant binding to plasma proteins found in Very small difference. Animal/Disease Models: Female and male SD (SD (Sprague-Dawley)) rats [3] Doses: 0, 30, 120 and 480 mg/kg Doses: po (po (oral gavage)) for 28 days Experimental Results: Blood pressure and serum uric acid diminished to 30 mg/kg; at 120 and 480 mg/kg, hemoglobin slightly diminished and S-GPT increased; the liver weight and serum magnesium concentration of male rats Dramatically increased, while the liver weight of female rats only increased slightly; in addition, it also induced Single cell necrosis of small groups of hepatocytes. In vivo animal studies with Tienilic acid have been conducted to study its diuretic, uricosuric, and antihypertensive effects. The compound was also used to study its hepatotoxic potential. Detailed protocols regarding dosage, treatment duration, and specific animal models are not extensively reported in the available literature. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Ticrynafen's known human metabolites include thiophene acid-S-oxide and thiophene-4,5-epoxide. Tienilic acid is rapidly metabolized and cleared. The primary metabolite of tienilic acid, 5-OH tienilic acid, is derived from a thiophene epoxide intermediate, which is likely responsible for the covalent binding and mechanism-based inactivation of CYP2C9. The compound's pharmacokinetics and metabolism have been extensively studied. |
| Toxicity/Toxicokinetics |
Tienilic acid was withdrawn from the market because of hepatotoxicity. The compound induces hepatotoxicity through the formation of reactive electrophilic metabolites by cytochrome P450 enzymes. The inhibition of CYP2C9 by tienilic acid can lead to the accumulation of reactive metabolites, which may cause cellular damage and hepatotoxicity.
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| References |
[1]. Takayoshi Nishiya, et al. Involvement of cytochrome P450-mediated metabolism in tienilic acid hepatotoxicity in rats. Toxicol Lett. 2008 Dec 15;183(1-3):81-9.
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| Additional Infomation |
Tienilic acid is an aromatic ketone, 2,3-dichlorophenoxyacetic acid, in which the hydrogen at the 4-position of the benzene ring is replaced by a thiophene carbonyl group. It was once a loop diuretic used to treat hypertension, but was withdrawn from the market in 1982 due to its association with hepatitis. It has loop diuretic, antihypertensive, and hepatotoxic effects. It belongs to the thiophene class, aromatic ketones, aromatic ethers, monocarboxylic acids, and dichlorobenzene class of compounds. Tienilic acid, also known as tecrolinine, is a diuretic with uric acid-lowering effects and was once used to treat hypertension. In 1982, some case reports in the United States suggested a link between tecrolinine and hepatitis, after which the drug was withdrawn from the market (Manier et al., 1982). It is a novel diuretic with uricosuric effects. It has been proposed for use as an antihypertensive drug. Drug Indications: For the treatment of hypertension.
Tienilic acid (ticrynafen) is a heterocyclic derivative of phenoxyacetic acid that acts as a suicide substrate at cytochrome P450 enzymes involved in drug metabolism. It is a good mechanism-based inhibitor of CYP2C9 and is commonly used as a diuretic, uricosuric, and antihypertensive agent. The compound is used in research to understand the metabolism and toxicity of thiophene-containing drugs. |
| Molecular Formula |
C13H8O4SCL2.C4H11NO3
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|---|---|
| Molecular Weight |
452.30626
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| Exact Mass |
329.952
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| CAS # |
40180-04-9
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| Related CAS # |
Tienilic acid; 40180-04-9
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| PubChem CID |
38409
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| Appearance |
White to light yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
534.6±50.0 °C at 760 mmHg
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| Melting Point |
148-149ºC
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| Flash Point |
277.1±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.632
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| LogP |
3.07
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
20
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| Complexity |
379
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CSC(=C1)C(=O)C2=C(C(=C(C=C2)OCC(=O)O)Cl)Cl
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| InChi Key |
AGHANLSBXUWXTB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H8Cl2O4S/c14-11-7(13(18)9-2-1-5-20-9)3-4-8(12(11)15)19-6-10(16)17/h1-5H,6H2,(H,16,17)
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| Chemical Name |
2-[2,3-dichloro-4-(thiophene-2-carbonyl)phenoxy]acetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
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. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~301.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (15.10 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Suspended solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (50.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2109 mL | 11.0544 mL | 22.1087 mL | |
| 5 mM | 0.4422 mL | 2.2109 mL | 4.4217 mL | |
| 10 mM | 0.2211 mL | 1.1054 mL | 2.2109 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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