| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
NLRP3; PGD2 ( IC50 = 0.1 mM ); Angiotensin II
|
|---|---|
| ln Vitro |
Significant immunomodulatory activity is exhibited by trojanlast, which also has the ability to prevent the formation of endotoxin-induced prostaglandin E2 (PGE2; IC50=~1–20 μM), thromboxane B2 (IC50=~10–50 μM), TGF-β1 (IC50=~100–200 μM), and IL-8 (IC50=~100 μM). With an IC50 of 10-40 μM and 2-20 μM, respectively, calatorilast prevents monocytes from producing leukotriene C4 or PGE2 when stimulated by A23187 [3]. Tranilast (10-200 μM) has dose-dependent antiproliferative effects in MCF-7 and MDA-MB-231 cell lines. In vitro, tamoxifen (1–20 μM) can also be enhanced in its anti-tumor activity on human breast cancer cells by trenilast (10–200 μM) [4]. HDMEC proliferation is inhibited by trenilast (12.5, 25, 50, and 100 μg/mL; 72 hours) [5].
|
| ln Vivo |
In mice, tranilast (300 mg/kg; orally administered twice daily for three days) suppresses angiogenesis in a dose-dependent manner [5].
|
| Cell Assay |
Cell proliferation assay [4]
Cell Types: MCF-7 and MDA-MB-231 Cell Tested Concentrations: 10, 20, 50, 100 and 200 μM Incubation Duration: 48 hrs (hours) Experimental Results: In both cell lines. Cell proliferation assay [5] Cell Types: Human dermal microvascular endothelial cells (HDMEC) Tested Concentrations: 12.5, 25, 50, 100 μg/mL Incubation Duration: 72 hrs (hours) Experimental Results: IC50 value is 44.3 μg/mL (136 μM). |
| Animal Protocol |
Animal/Disease Models: Nineweeks old male C57BL/6 mice [5]
Doses: 300 mg/kg Route of Administration: Orally administered twice a day for 3 days Experimental Results: Inhibition of angiogenesis induced by VEGF in Matrigel; at 300 mg/kg A significant inhibition of 58% was observed at the dose. The ED50 value and 95% confidence limit are 165mg/kg and 162±169mg/kg respectively. |
| ADME/Pharmacokinetics |
Following oral administration in humans, peak plasma concentrations of Tranilast are achieved within 2 to 3 hours. The elimination half-life is approximately 8.6 hours. Drug levels are significantly reduced by 24 hours and fall below the detection limit after 48 hours .
Tranilast is primarily eliminated via urine, with the majority of the dose excreted within 96 hours of administration . The main metabolic pathway is the formation of a glucuronide conjugate. The principal metabolite is the 4-O-demethylated product conjugated with sulfate and glucuronic acid . In vitro studies using human liver microsomes and recombinant enzymes indicate that the oxidative metabolism of Tranilast involves multiple cytochrome P450 (CYP) isoforms. These include CYP2C9, CYP2C18, CYP2C8, CYP1A2, CYP3A4, and CYP2D6, with CYP2C9 being identified as a primary contributor . In vitro studies have elucidated the glucuronidation pathway of Tranilast. The glucuronidation is primarily catalyzed by the UGT1A1 enzyme in both human liver and intestine. The kinetic parameters (Km) for this activity were determined to be 51.5 μM in human liver microsomes, 50.6 μM in human jejunum microsomes, and 38.0 μM for recombinant UGT1A1. The corresponding Vmax values were 10.4, 42.9, and 19.7 pmol/min/mg protein, respectively. Calculated intrinsic clearance suggested that glucuronidation activity is 2.5-fold higher in the liver than in the intestine . In vitro metabolism studies also determined the kinetics for the formation of the phase I metabolite, 4-demethyltranilast (N-3). In human liver microsomes, the Km and Vmax for N-3 formation were 37.1 μM and 27.6 pmol/min/mg protein, respectively . Tranilast glucuronosyltransferase activity was found to be strongly inhibited by its phase I metabolite (N-3), suggesting a potential for the metabolite to affect the parent drug's metabolism . |
| Toxicity/Toxicokinetics |
In animal studies, Tranilast has been shown to have teratogenic effects, and therefore it is contraindicated in pregnant women .
Clinically, Tranilast can cause hepatic and renal adverse reactions. Hepatic effects may include jaundice and significant elevations in liver enzymes such as AST, ALT, and AL-P, potentially leading to liver dysfunction or hepatitis. Renal effects can include increases in blood urea nitrogen (BUN) and serum creatinine . Other observed adverse reactions include urinary system effects (e.g., frequency, dysuria, hematuria), hematological effects (e.g., decreased red blood cell count and hemoglobin, leukopenia, thrombocytopenia), gastrointestinal disturbances (e.g., anorexia, nausea, vomiting, abdominal pain), and central nervous system effects (e.g., headache, drowsiness, dizziness) . In vitro studies show that Tranilast and its phase I metabolite (N-3) strongly inhibit bilirubin glucuronosyltransferase (UGT1A1) activity. This inhibition is suggested as the mechanism for the hyperbilirubinemia observed in some patients during clinical trials, potentially linked to UGT1A1 genotype . In a clinical safety study involving patients with advanced heart failure and muscular dystrophy, Tranilast administered orally at 100 mg three times daily for 6 months was reported to have no serious adverse events related to the drug, aside from diarrhea, a known side effect . The material safety data sheet for Tranilast classifies it as an oral acute toxin (Category 4) and advises caution to avoid inhalation, skin contact, and eye contact . Standard first aid measures include rinsing skin or eyes with large amounts of water and seeking medical attention if necessary . The toxicological effects have not been thoroughly studied . |
| References |
|
| Additional Infomation |
Tranilast is an amidobenzoic acid that is anthranilic acid in which one of the anilino hydrogens is replaced by a 3,4-dimethoxycinnamoyl group. It has a role as an anti-asthmatic drug, a nephroprotective agent, an anti-allergic agent, a calcium channel blocker, an antineoplastic agent, an aryl hydrocarbon receptor agonist and a hepatoprotective agent. It is a member of cinnamamides, a dimethoxybenzene, an amidobenzoic acid and a secondary carboxamide. It is functionally related to an anthranilic acid.
Tranilast is an antiallergic drug developed by Kissei Pharmaceuticals. In 1982, it was approved in Japan and South Korea for the management of bronchial asthma. Indications for keloid and hypertrophic scar were added in 1993. It has been used for the treatment of allergic disorders such as asthma, allergic rhinitis and atopic dermatitis.
|
| Molecular Formula |
CL-.NA+
|
|---|---|
| Molecular Weight |
58.4428
|
| Exact Mass |
349.092
|
| Elemental Analysis |
C, 61.89; H, 4.62; N, 4.01; Na, 6.58; O, 22.90
|
| CAS # |
104931-56-8
|
| Related CAS # |
trans-Tranilast;70806-55-2;Tranilast;53902-12-8
|
| PubChem CID |
23669590
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
25
|
| Complexity |
470
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C([O-])C1=CC=CC=C1NC(/C=C/C2=CC=C(OC)C(OC)=C2)=O.[Na+]
|
| InChi Key |
KZGHWWBBHZLTTA-VRTOBVRTSA-M
|
| InChi Code |
InChI=1S/C18H17NO5.Na/c1-23-15-9-7-12(11-16(15)24-2)8-10-17(20)19-14-6-4-3-5-13(14)18(21)22;/h3-11H,1-2H3,(H,19,20)(H,21,22);/q;+1/p-1/b10-8+;
|
| Chemical Name |
sodium;2-[[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino]benzoate
|
| Synonyms |
Tranilast sodium; Tranilast (Sodium); 104931-56-8; Sodium 2-(3-(3,4-dimethoxyphenyl)acrylamido)benzoate; sodium;2-[[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino]benzoate;
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 17.1116 mL | 85.5578 mL | 171.1157 mL | |
| 5 mM | 3.4223 mL | 17.1116 mL | 34.2231 mL | |
| 10 mM | 1.7112 mL | 8.5558 mL | 17.1116 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05626829 | Recruiting | Drug: Tranilast | Nasopharyngeal Carcinoma Recurrent Cancer |
Jian Guan | July 20, 2022 | Phase 2 |
| NCT03923140 | Recruiting | Drug: Tranilast | Cryopyrin-Associated Periodic Syndromes |
Peking Union Medical College Hospital |
May 23, 2019 | Phase 2 |
| NCT01003613 | Completed | Drug: Tranilast, and Tissucol Drug: Beriplast P |
Pterygium | Gildasio Castello de Almeida Junior |
February 2009 | Phase 3 |
| NCT00882024 | Completed | Drug: Tranilast Drug: Placebo |
Active Rheumatoid Arthritis | Nuon Therapeutics, Inc. | March 2009 | Phase 2 |
| NCT01052987 | Completed | Drug: Tranilast Drug: Allopurinol |
Gout Hyperuricemia |
Nuon Therapeutics, Inc. | January 2010 | Phase 2 |
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