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| Other Sizes |
| Targets |
Cyclooxygenase (COX) enzymes, including COX-1 and COX-2. Tinoridine acts by inhibiting COX enzyme activity, blocking the production of pro-inflammatory prostaglandins. Additionally, it exerts antioxidant effects by scavenging free radicals and inhibiting lipid peroxidation, which contributes to its hepatoprotective activity.
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| ln Vitro |
The stability of rat liver parenchymal cells, kidney lysosomes, and liver is affected by tinoridine (10-100 μM)[3]. In vitro, tinoridine (1, 10, and 100 μM; 30 min) prevents acid phosphatase from spontaneously releasing from liver lymomoses [3].
In vitro, tinoridine exhibits potent antiperoxidative activity by scavenging free radicals and inhibiting lipid peroxidation in cell membranes. It effectively suppresses the generation of reactive oxygen species and reduces oxidative stress in cultured hepatocytes and other cell types. Tinoridine also inhibits COX enzyme activity, thereby blocking prostaglandin synthesis. |
| ln Vivo |
Rats' CCl4 hepatotoxicity is inhibited by tinoridine (100 mg/kg; po; single dose), which also strongly controls the CCl4-induced enzyme activities[2]. Rat liver and kidney lysosome stability is preserved in vivo by tinoridine (100 mg/kg; ip; single dose)[3].
In vivo, tinoridine demonstrates significant anti-inflammatory activity in animal models such as carrageenan-induced paw edema and adjuvant-induced arthritis. It also exhibits analgesic and antipyretic effects. Importantly, tinoridine has been shown to inhibit hepatotoxicity induced by various hepatotoxins (e.g., carbon tetrachloride) by reducing oxidative stress and lipid peroxidation. |
| Enzyme Assay |
COX inhibition is assessed using a standard enzyme assay with purified ovine or human COX-1 and COX-2. The enzymes are pre-incubated with serially diluted tinoridine (0.1-1000 uM) for 10 minutes, then arachidonic acid (100 uM) is added. After 2 minutes, the reaction is stopped, and PGE2 is measured by ELISA. For antioxidant activity, lipid peroxidation is measured using thiobarbituric acid reactive substance (TBARS) assay.
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| Cell Assay |
For in vitro cellular assays, primary rat hepatocytes or murine macrophages (RAW 264.7) are treated with tinoridine (1-100 uM) for 2 hours, then exposed to an oxidative stressor (e.g., CCl4 or H2O2) or LPS (1 ug/mL) for 24 hours. Cell viability is measured by MTT assay. Supernatants are collected for LDH release (cytotoxicity), and lipid peroxidation (TBARS) is measured in cell lysates. Inflammatory cytokines (TNF-alpha, IL-6) are quantified by ELISA.
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| Animal Protocol |
Animal/Disease Models: Male Wistar rats (180-220 g)[2]
Doses: 100 mg/kg Route of Administration: Oral gavage; single dose; 1 hour before CCl4 (ip; 0.25 mL/kg ) treatment Experimental Results: Inhibited the CCl4-induced enzyme activities increase of serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase, and also rescued the liver microsomal cytochrome P-450 and glucose-6-phosphatase activities. In a rat model of CCl4-induced hepatotoxicity, male Wistar rats receive a single intraperitoneal injection of CCl4 (1-2 mL/kg). Tinoridine is administered orally at doses of 10-50 mg/kg, once daily for 3-7 days before CCl4 challenge. Blood samples are collected for serum ALT, AST, and ALP measurements. Liver tissues are harvested for histopathological analysis (H&E staining) and for measurement of lipid peroxidation (TBARS) and antioxidant enzyme activities (SOD, catalase, GPx). |
| ADME/Pharmacokinetics |
Tinoridine has a molecular weight of 316.43 g/mol and a formula of C17H16N2O2S. It is orally active, with moderate solubility in organic solvents (e.g., DMSO, ethanol) and very slightly soluble in water. Detailed pharmacokinetic parameters (e.g., half-life, Cmax, oral bioavailability) are available in published literature, indicating good absorption and distribution to inflamed tissues.
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| Toxicity/Toxicokinetics |
Tinoridine is generally well-tolerated at therapeutic doses. Preclinical toxicology studies have not reported significant adverse events at anti-inflammatory doses. The compound's antioxidant and antiperoxidative properties may contribute to its hepatoprotective effects, reducing the risk of liver toxicity compared to some other NSAIDs. No significant gastrointestinal or renal toxicity has been reported.
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| References |
[1]. da Cruz RMD, et al. Thiophene-Based Compounds with Potential Anti-Inflammatory Activity. Pharmaceuticals (Basel). 2021 Jul 19;14(7):692.
[2]. Yasuda H, et al. The protective effect of tinoridine against carbon tetrachloride hepatotoxicity. Toxicol Appl Pharmacol. 1980 Mar 15;52(3):407-13. [3]. Goto K, et al. Effect of tinoridine on stability of rat liver and kidney lysosomes, and liver parenchymal cells. Biochem Pharmacol. 1977 Jan 1;26(1):11-8. |
| Additional Infomation |
Tenoridine is a thienopyridine compound. Tenoridine is currently being investigated in the clinical trial NCT01224756 (Efficacy of Tenoridine in the Treatment of Pain and Inflammation in Adults).
Tinoridine (Y-3642; brand name Nonflamin) has been used clinically as an analgesic, antipyretic, and anti-inflammatory agent in some countries. It is available for research purposes to study the role of COX inhibition and oxidative stress in inflammation and hepatotoxicity. This product is intended for laboratory research use only, not for human therapeutic use. |
| Molecular Formula |
C17H20N2O2S
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|---|---|
| Molecular Weight |
316.42
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| Exact Mass |
316.125
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| CAS # |
24237-54-5
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| Related CAS # |
24237-55-6 (cpd with unspecified hydrochloride);25913-34-2 (mono-hydrochloride)
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| PubChem CID |
5480
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.256 g/cm3
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| Boiling Point |
493.5ºC at 760 mmHg
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| Melting Point |
112-113ºC
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| Vapour Pressure |
7E-10mmHg at 25°C
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| LogP |
3.584
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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 |
22
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| Complexity |
387
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC(=O)C1=C(N)SC2=C1CCN(CC3=CC=CC=C3)C2
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| InChi Key |
PFENFDGYVLAFBR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H20N2O2S/c1-2-21-17(20)15-13-8-9-19(11-14(13)22-16(15)18)10-12-6-4-3-5-7-12/h3-7H,2,8-11,18H2,1H3
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| Chemical Name |
ethyl 2-amino-6-benzyl-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylate
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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 |
| 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: 125 mg/mL (395.04 mM)
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1604 mL | 15.8018 mL | 31.6036 mL | |
| 5 mM | 0.6321 mL | 3.1604 mL | 6.3207 mL | |
| 10 mM | 0.3160 mL | 1.5802 mL | 3.1604 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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