| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Phosphodiesterase (PDE), particularly PDE4. Tibenelast sodium is a PDE inhibitor.
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| ln Vitro |
In healthy male volunteers, the effects of the phosphodiesterase inhibitor Tibenelast and a placebo were examined in relation to changes in heart rate, cAMP, and norepinephrine levels brought on by isoproterenol. While norepinephrine and cAMP levels remain unchanged with medication, Tillest enhances the heart rate response to isoproterenol infusion [1].
In vitro, Tibenelast shows moderate activity against lung and stomach PDE while being a very weak inhibitor of cardiac PDE. It is 10× more potent than aminophylline (i.v.) in normalizing pulmonary function. Tibenelast is 100× more potent than aminophylline in inhibiting superoxide generation from human neutrophils. The compound does not inhibit arachidonic acid metabolism enzymes, enabling clean PDE4-mechanistic readouts. |
| ln Vivo |
Strong oral active substance tibenelast effectively prevents anaphylactic shock brought on by high-dosage antigen aerosols. Bronchoconstriction was seen with a decrease in dynamic compliance (Cdyn) and an increase in lung resistance (RL) after a lesser aerosol challenge of 0.05 mg/mL. Tibasilast 25 mg/kg given orally stopped these alterations. Tibenelast administered intravenously is ten times more effective than aminophylline; when combined with epinephrine, tibenelast at a dose of 1 mg/kg helps restore lung function. Combining tibasilast with epinephrine improves its oral dose-response profile. Treatment for asthma and other respiratory conditions may benefit with tilbest [2].
In vivo, Tibenelast is a potent orally active compound against anaphylactic shock induced by high dose antigen aerosol. The oral ED₅₀ is 25 mg/kg in guinea pig anaphylaxis models. When a lower aerosol challenge is employed, bronchoconstriction is observed with a concomitant increase in lung resistance and a fall in dynamic compliance. Tibenelast may be of significant value in the treatment of asthma and other respiratory diseases. |
| Enzyme Assay |
Non-cell enzyme assays for Tibenelast are performed using purified phosphodiesterase enzymes from various tissues (lung, stomach, cardiac). PDE activity is measured by the conversion of [³H]cAMP or [³H]cGMP to the corresponding nucleotide monophosphates. Enzymes are incubated with the substrate and varying concentrations of Tibenelast (0.001-100 μM) in assay buffer at 30°C for 30 minutes. The reaction is terminated by boiling, and the products are separated by ion-exchange chromatography. IC₅₀ values are calculated from dose-response curves to assess PDE isoform selectivity.
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| Cell Assay |
Cellular assays for Tibenelast are performed using human neutrophils or other immune cells. Cells are stimulated with phorbol myristate acetate (PMA) or other activators to induce superoxide generation. Tibenelast at concentrations ranging from 0.01-100 μM is added prior to stimulation. Superoxide production is measured by the reduction of cytochrome c or by luminol-enhanced chemiluminescence. IC₅₀ values for inhibition of superoxide generation are calculated. Cell viability is assessed by trypan blue exclusion or MTT assays.
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| Animal Protocol |
In vivo animal studies are conducted in guinea pig models of anaphylaxis. Guinea pigs are sensitized with antigen and challenged with antigen aerosol. Tibenelast is administered orally at doses ranging from 1-50 mg/kg prior to challenge. Airway resistance and dynamic compliance are measured using whole-body plethysmography. The protective effect against anaphylactic shock is evaluated. Bronchoalveolar lavage fluid is collected to assess inflammatory cell infiltration.
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| ADME/Pharmacokinetics |
Tibenelast sodium has a molecular weight of 288.30 and a molecular formula of C13H13NaO4S. It is also known as LY 186655. The compound is supplied as a solid powder with >98% purity and is stable at -20°C for up to 3 years. It is soluble in DMSO.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Tibenelast are limited. The compound's selectivity for lung/stomach PDE over cardiac PDE suggests a reduced risk of cardiac side effects compared to non-selective PDE inhibitors. No significant organ-specific toxicity has been reported in clinical trials. Standard safety pharmacology studies have been conducted.
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| References |
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| Additional Infomation |
Tibenelast sodium is a PDE inhibitor that was advanced to Phase II clinical trials for the treatment of asthma and other respiratory diseases. It exhibits a distinct selectivity profile: moderately active against lung and stomach PDE while being a weak inhibitor of cardiac PDE. Tibenelast is not currently approved for clinical use.
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| Molecular Formula |
C13H13O4S-.NA+
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|---|---|
| Molecular Weight |
288.29472
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| Exact Mass |
288.043
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| CAS # |
105102-18-9
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| PubChem CID |
23700081
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| Appearance |
White to off-white solid powder
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| Boiling Point |
440.8ºC at 760mmHg
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| Flash Point |
220.4ºC
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| Vapour Pressure |
1.52E-08mmHg at 25°C
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| LogP |
2.062
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
19
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| Complexity |
302
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ILEWAUWOUIHKID-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C13H14O4S.Na/c1-3-16-9-5-8-6-12(13(14)15)18-11(8)7-10(9)17-4-2;/h5-7H,3-4H2,1-2H3,(H,14,15);/q;+1/p-1
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| Chemical Name |
sodium;5,6-diethoxy-1-benzothiophene-2-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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~50 mg/mL (~173.44 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.67 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.21 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4687 mL | 17.3436 mL | 34.6873 mL | |
| 5 mM | 0.6937 mL | 3.4687 mL | 6.9375 mL | |
| 10 mM | 0.3469 mL | 1.7344 mL | 3.4687 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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