PGD2/rostaglandin D2 ( IC50 = 0.1 mM ); NLRP3; Angiotensin II
Tranilast targets the release of transforming growth factor-beta 1 (TGF-β1) from keloid fibroblasts [1]
Tranilast targets the release of interleukin-1 beta (IL-1β) and prostaglandin E2 (PGE2) from human monocytes-macrophages [2]
Tranilast targets platelet-derived growth factor-BB (PDGF-BB)-induced migration/proliferation and TGF-β1-induced extracellular matrix synthesis in vascular smooth muscle cells [3]
Tranilast targets chymase (mast cell-derived serine endopeptidase) expression and activity in vascular tissues , with no effect on angiotensin-converting enzyme (ACE) [5]

Tranilast is an anti-allergic medication that prevents mast cells from releasing chemicals like prostaglandins and histamine, which reduces the production of collagen by fibroblasts that are derived from keloid tissues. Trenilast (3–300 mM) inhibits the production of collagen by fibroblasts from hypertrophic and keloid scar tissue, but not by fibroblasts from healthy skin. Tranistin (30–300 mM) prevents keloid fibroblasts from releasing transforming growth factor (TGF)–beta 1, which increases keloid fibroblasts' ability to synthesize collagen.[1] Tranilast helps with hypertrophic scars and keloids, which are caused by fibroblasts that proliferate abnormally and accumulate excessive amounts of collagen. The release of PGE2, IL-1 beta, and TGF-beta 1 from human monocytes/macrophages is inhibited by troglilast.[2] Tranalilast suppresses the migration that is induced by platelet-derived growth factor-BB (PDGF-BB), TGF-beta1, fetal bovine serum (FBS), and PDGF-BB. The synthesis of collagen and glycosaminoglycan is induced by TGF-beta 1 and spontaneous collagen synthesis is inhibited by tanninlast.[3]

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1. In cultured keloid and hypertrophic scar fibroblasts, Tranilast (3–300 μM) suppressed collagen synthesis, but had no inhibitory effect on collagen synthesis of healthy human skin fibroblasts; Tranilast (3–100 μM) did not inhibit prolyl hydroxylase (the rate-limiting enzyme in collagen synthesis) activity, and Tranilast (30–300 μM) inhibited the release of TGF-β1 from keloid fibroblasts [1]
2. In cultured human monocytes-macrophages, Tranilast inhibited the release of TGF-β1, IL-1β and PGE2; exogenous TGF-β1 (25–200 pM) enhanced collagen synthesis by normal skin fibroblasts, IL-1 (0.1–1 U/ml) increased fibroblast proliferation and decreased collagen synthesis, and PGE2 (2 μg/ml) enhanced fibroblast collagen synthesis [2]
3. In cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR), Tranilast (30–300 μM) inhibited cell proliferation stimulated by fetal bovine serum (FBS), TGF-β1 and PDGF-BB; it also inhibited PDGF-BB-induced migration of SHR-VSMC, and suppressed spontaneous collagen synthesis as well as TGF-β1-induced synthesis of collagen and glycosaminoglycans in SHR-VSMC [3]
4. In cultured cardiac fibroblasts, Tranilast (30 μM) reduced TGF-β1-induced 3[H]-hydroxyproline incorporation by 58% (p<0.01), indicating the inhibition of TGF-β1-induced matrix production [4]

Tranilast reduces 3[H]-hydroxyproline incorporation induced by TGF-beta1 by 58% in the diabetic heart of rats. In the diabetic heart of rats, tranilast reduces phospho-Smad2 by 37% and attenuates cardiac fibrosis. [4] In the canine carotid artery, tranilast treatment completely stops the increase in chymaselike activity, lowers chymase mRNA levels by 43%, and lowers the carotid intima/media ratio by 63%.[5]

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1. In (mRen-2)27 diabetic rats (8 weeks after streptozotocin-induced diabetes), treatment with Tranilast attenuated cardiac fibrosis by 37% (p<0.05) at 16 weeks, accompanied by a reduction in the abundance of phosphorylated Smad2 (p<0.01); the antifibrotic effect was observed despite persistent hyperglycemia and hypertension in the rats [4]
2. In beagle dogs with balloon-injured carotid artery, oral administration of Tranilast (50 mg/kg twice daily) for 2 weeks before and 4 weeks after injury completely prevented the increase in chymase-like activity, reduced chymase mRNA levels by 43%, and decreased the carotid intima/media ratio by 63%; it also completely prevented the increase in mast cell count in the adventitia of injured arteries, with no effect on vascular ACE activity and mRNA levels [5]

1. Prolyl hydroxylase activity assay: Enzyme extracts were prepared from relevant cellular or tissue samples, and the prolyl hydroxylase reaction system was constructed by adding the specific substrate of the enzyme. Different concentrations of Tranilast (3–100 μM) were added to the reaction system, and after incubation for a set period, the enzyme activity was detected by relevant biochemical methods to evaluate whether tranilast had an inhibitory effect on prolyl hydroxylase [1]
2. Chymase-like activity assay: Tissue homogenates were prepared from balloon-injured dog carotid arteries, and the chymase-like activity in the homogenates was measured using dedicated substrates and reaction conditions. The activity of angiotensin-converting enzyme (ACE) was also detected with corresponding methods to compare the differential effects of Tranilast on chymase and ACE [5]
3. ACE activity and mRNA assay: Vascular tissue homogenates from injured dog carotid arteries were used to detect ACE activity via biochemical assays, and the mRNA levels of ACE were analyzed by molecular biology techniques to determine the influence of Tranilast treatment on ACE expression and activity [5]

1. Keloid/hypertrophic scar fibroblast assay: Fibroblasts were isolated from human keloid, hypertrophic scar and healthy skin tissues, and cultured in vitro under optimal conditions. The cultured fibroblasts were treated with different concentrations of Tranilast (3–300 μM), and collagen synthesis was detected by biochemical methods; the release of TGF-β1 from keloid fibroblasts was measured with specific kits, and prolyl hydroxylase activity was assessed to clarify the mechanism of tranilast’s action [1]
2. Human monocytes-macrophages assay: Human monocytes-macrophages were isolated and cultured in vitro, then treated with Tranilast; the levels of TGF-β1, IL-1β and PGE2 released into the culture medium were determined by corresponding detection methods. Meanwhile, normal skin fibroblasts were cultured and treated with exogenous TGF-β1, IL-1 and PGE2, and fibroblast collagen synthesis and cell proliferation were detected to analyze the biological effects of these mediators [2]
3. SHR vascular smooth muscle cell assay: Vascular smooth muscle cells were isolated from spontaneously hypertensive rats (SHR) and cultured in vitro. The cells were stimulated with FBS, TGF-β1 or PDGF-BB and co-treated with Tranilast (30–300 μM); cell proliferation was detected by proliferation assays, cell migration was evaluated by migration models, and the synthesis of collagen and glycosaminoglycans was measured by biochemical methods to determine the inhibitory effects of tranilast [3]
4. Cardiac fibroblast assay: Cardiac fibroblasts were isolated and cultured in vitro, then treated with TGF-β1 alone or in combination with Tranilast (30 μM). The incorporation of 3[H]-hydroxyproline was detected to reflect collagen and extracellular matrix synthesis, thereby evaluating the inhibitory effect of tranilast on TGF-β1-induced matrix production [4]

1. Diabetic cardiomyopathy rat model protocol: (mRen-2)27 rats were injected with streptozotocin to establish diabetic models. After 8 weeks of diabetes onset (with established disease), the rats were treated with Tranilast until 16 weeks after diabetes induction. Cardiac tissues were collected, cardiac fibrosis was assessed by pathological staining, and the abundance of phosphorylated Smad2 was measured by molecular biology techniques to evaluate the antifibrotic effect of tranilast [4]
2. Balloon-injured dog carotid artery model protocol: Beagle dogs were orally administered Tranilast at a dose of 50 mg/kg twice daily, with administration starting 2 weeks before balloon injury of the carotid artery and continuing for 4 weeks after injury. Four weeks post-injury, carotid artery tissues were harvested to detect chymase mRNA levels, chymase-like activity, ACE activity, adventitial mast cell count, and carotid intima/media ratio, so as to evaluate the effect of tranilast on neointima formation [5]

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 .

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 .

[1]. Jpn J Pharmacol . 1992 Oct;60(2):91-6.

[2]. Jpn J Pharmacol . 1992 Oct;60(2):85-90.

[3]. Atherosclerosis . 1995 Dec;118(2):213-21.

[4]. Cardiovasc Res . 2005 Feb 15;65(3):694-701.

[5]. Circulation . 1999 Mar 2;99(8):1084-90.

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, and its structure is similar to 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, the indication for keloids and hypertrophic scars was added. It is also used to treat allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis.

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Drug Indications
Used to treat bronchial asthma, keloids and hypertrophic scars, as well as allergic diseases such as asthma, allergic rhinitis and atopic dermatitis.

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1. Tranilast is an anti-allergic drug that inhibits the release of histamine, prostaglandins and other mediators from mast cells and is used to treat fibrotic skin diseases such as keloids and hypertrophic scars[1].
2. Tranilast inhibits collagen synthesis in fibroblasts of keloids and hypertrophic scars by inhibiting the release of TGF-β1 from fibroblasts themselves, rather than by inhibiting prolyl hydroxylase. Activity[1]
3. Tranilast inhibits fibroblast collagen synthesis by suppressing the production of TGF-β1 and PGE2 by inflammatory cells (e.g., monocytes-macrophages) and inhibits fibroblast proliferation by reducing the production of IL-1 by these inflammatory cells[2]
4. Tranilast may prevent restenosis after percutaneous coronary angioplasty by inhibiting the proliferation, migration and extracellular matrix synthesis of vascular smooth muscle cells[3]
5. Tranilast exerts an anti-fibrotic effect in diabetic hearts by reducing TGF-β activity, thereby reducing cardiac matrix deposition in experimental diabetes[4]
6. Tranilast inhibits the formation of chymotrypsin-dependent angiotensin II (ANG II) by inhibiting the expression and activity of chymotrypsin genes in damaged vascular tissue, thereby inhibiting the proliferation of vascular endothelial cells[4] and helping to prevent the formation of neointima after vascular injury[5]

C18H17NO5

327.34

327.11

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

53902-12-8

trans-Tranilast; 70806-55-2; Tranilast sodium; 104931-56-8

5282230

Light yellow to green yellow solid powder

1.3±0.1 g/cm3

585.5±50.0 °C at 760 mmHg

166-168ºC

307.9±30.1 °C

0.0±1.7 mmHg at 25°C

1.648

4.36

2

5

6

24

464

0

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

MK-341; MK 341; MK341; SB-252218; SB 252218; SB252218; Tranilast; 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)

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) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
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 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.

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Solubility in Formulation 3: ≥ 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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Solubility in Formulation 4: 5%DMSO+ Corn oil: 3.5mg/ml (10.69mM)

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Solubility in Formulation 5: 5 mg/mL (15.28 mM) in 30 % SBE-β-CD (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.

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Solubility in Formulation 6: 4 mg/mL (12.22 mM) in 1.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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