PGD2/rostaglandin D2 ( IC50 = 0.1 mM ); Angiotensin II <
Tranilast trans- targets multiple proteins and signaling pathways. It is known to inhibit the production of prostaglandin D2 (PGD2) with an IC₅₀ of 0.1 mM and acts as an Angiotensin II receptor antagonist. It also inhibits the production of interleukin-6 (IL-6) in endothelial cells and reduces collagen synthesis in fibroblasts. Its anti-fibrotic effects are mediated through the suppression of TGF-β signaling and fibroblast activation. Tranilast trans- has been shown to inhibit the growth of neurofibroma cells. Additionally, it functions as a calcium channel blocker and an aryl hydrocarbon receptor agonist, contributing to its diverse pharmacological profile. The compound's ability to modulate inflammatory and fibrotic pathways makes it a promising candidate for treating conditions such as hypertrophic scars, keloids, and pulmonary and renal fibrosis.

In vitro studies have demonstrated that Tranilast trans- effectively inhibits the release of inflammatory mediators such as histamine, prostaglandins, and cytokines from mast cells and other immune cells. It suppresses the activation of fibroblasts and reduces collagen synthesis, which is crucial for its anti-fibrotic activity. The compound also inhibits the production of interleukin-6 in endothelial cells and shows antitumor activity by inhibiting the growth of neurofibroma cells. Its calcium channel blocking activity and aryl hydrocarbon receptor agonism have been characterized in various cell-based assays. The trans-isomer is the active form of the drug, with the cis-isomer being significantly less active. Detailed IC₅₀ values for its various activities, such as the 0.1 mM for PGD2 inhibition, have been reported.

In vivo, Tranilast trans- has been clinically used for the treatment of bronchial asthma, allergic rhinitis, and atopic dermatitis. Its therapeutic benefits in these conditions are attributed to its anti-allergic and anti-inflammatory properties. The compound has also been shown to be effective in reducing the formation of keloids and hypertrophic scars, demonstrating its clinical utility in fibrotic conditions. Preclinical studies have explored its nephroprotective and hepatoprotective effects, suggesting broader therapeutic applications. The drug's ability to modulate TGF-β signaling and suppress fibroblast activation contributes to its efficacy in fibrotic diseases. Despite its approval in Japan and South Korea, Tranilast is not widely used globally, and its clinical use is primarily in Asia.

In vitro non-cell enzyme/receptor binding assays for Tranilast trans- typically involve measuring its inhibition of prostaglandin D2 (PGD2) synthase or its binding to the Angiotensin II receptor. These assays use purified enzymes or receptor-containing membrane preparations. The compound is incubated with the enzyme or receptor and a labeled substrate or ligand, and the inhibition of activity or displacement of binding is quantified. IC₅₀ values, such as the 0.1 mM for PGD2 inhibition, are determined from dose-response curves. The compound's interaction with the aryl hydrocarbon receptor can also be assessed using reporter gene assays in cell-free systems. These assays provide quantitative data on the compound's direct interactions with its molecular targets.

In vitro cell-based assays for Tranilast trans- use various cell lines to evaluate its anti-inflammatory, anti-fibrotic, and antitumor activities. For anti-inflammatory studies, mast cells or endothelial cells are stimulated with relevant triggers, and the production of cytokines (e.g., IL-6) and other inflammatory mediators is measured by ELISA. For anti-fibrotic studies, fibroblasts are treated with TGF-β in the presence or absence of the compound, and collagen synthesis is assessed by measuring hydroxyproline content or by Western blotting for collagen proteins. Cell viability and proliferation are assessed using MTT or similar assays to evaluate its antitumor effects on neurofibroma cells.

In vivo animal studies for Tranilast trans- have been conducted in models of allergic inflammation, fibrosis, and cancer. In models of bronchial asthma, the compound is administered orally to sensitized animals, and its effects on airway hyperresponsiveness and inflammatory cell infiltration are assessed. In models of fibrosis, such as bleomycin-induced pulmonary fibrosis or skin wound healing models, the compound's ability to reduce collagen deposition and scar formation is evaluated. Its antitumor efficacy has been studied in xenograft models using neurofibroma or other cancer cell lines. Pharmacokinetic and toxicological studies have also been performed to support its clinical use.

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 .
Tranilast trans- has a molecular weight of 327.33 g/mol and a molecular formula of C₁₈H₁₇NO₅. It is a white to off-white powder that is soluble in DMSO and ethanol but practically insoluble in water. The compound is stable under normal storage conditions and should be stored at room temperature, protected from light and moisture. Its pharmacokinetic profile is characterized by good oral absorption, with peak plasma concentrations reached within a few hours. It is extensively metabolized in the liver, primarily via glucuronidation, and excreted in the urine and feces. The compound has a relatively short half-life, requiring multiple daily dosing for therapeutic effects.

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 .
Tranilast trans- is generally well-tolerated, with a safety profile established through clinical use. Common side effects include gastrointestinal disturbances such as nausea, vomiting, and abdominal discomfort. Rare but more serious adverse effects include liver enzyme elevation and allergic reactions. The compound is contraindicated in patients with a history of hypersensitivity to Tranilast or any of its components. Its use during pregnancy and lactation is not recommended due to insufficient safety data. The compound's safety in pediatric patients has not been fully established. Long-term safety studies have not revealed significant carcinogenic or mutagenic risks.

[1]. Inhibitory Effect of Tranilast on Prostaglandin D Synthetase. Biochem Pharmacol. 1989 Aug 15;38(16):2673-6.

Tranilast is an aminobenzoic acid compound with a structure similar to anthranilic acid, except that one aniline hydrogen atom is replaced by a 3,4-dimethoxycinnamoyl group. It possesses various pharmacological effects, including anti-asthmatic, nephroprotective, anti-allergic, calcium channel blocker, antitumor, aryl hydrocarbon receptor agonist, and hepatoprotective agent. Tranilast belongs to the cinnamicamide, dimethoxybenzene, aminobenzoic acid, and secondary amide classes. Its function is related to that of anthranilic acid. Tranilast is an anti-allergic drug developed by Gisele Pharmaceuticals. In 1982, it was approved in Japan and South Korea for the treatment of bronchial asthma. In 1993, its indication for the treatment of keloids and hypertrophic scars was added. It has also been used to treat allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis.

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Drug Indications
For the treatment of bronchial asthma, keloids and hypertrophic scars, as well as allergic diseases such as asthma, allergic rhinitis and atopic dermatitis.
Tranilast trans- (trans-MK-341) is an antiallergic drug approved in Japan and South Korea since 1982 for bronchial asthma, with additional indications for keloids and hypertrophic scars added in 1993. It is a multi-targeted compound that inhibits the release of inflammatory mediators, suppresses fibroblast activation and TGF-β signaling, and exhibits calcium channel blocking and aryl hydrocarbon receptor agonist activities. Its anti-fibrotic properties make it a subject of ongoing research for conditions such as pulmonary and renal fibrosis. Despite its limited global use, Tranilast remains a valuable tool for studying allergic and fibrotic diseases. It is not approved for use in the United States or Europe.

C18H17NO5

327.331285238266

327.111

C, 66.05; H, 5.23; N, 4.28; O, 24.44

70806-55-2

Tranilast; 53902-12-8; Tranilast sodium; 104931-56-8

5282230

White to off-white solid powder

3.703

2

5

6

24

464

0

O=C(O)C1=CC=CC=C1NC(/C=C/C2=CC(OC)=C(OC)C=C2)=O

NZHGWWWHIYHZNX-CSKARUKUSA-N

InChI=1S/C18H17NO5/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)/b10-8+

2-[[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino]benzoic acid

Tranilast; SB252218; SB-252218; SB 252218; MK 341; MK341; MK-341; trans-Tranilast; brand name: Rizaben; Tranilastum; Tranpro

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)

DMSO: 65~100 mg/mL (198.6~305.5 mM)
Ethanol: ~4 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.64 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)