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Chemical Structure| 53902-12-8 Chemical Structure| 53902-12-8

Structure of Tranilast
CAS No.: 53902-12-8

Chemical Structure| 53902-12-8

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Tranilast can antagonize angiotensin II and also work as an antiallergic agent. It showed inhibitory effect for NLRP3 inflammasome but not for NLRC4 or AIM2 inflammasome. Tranilast impaired the endogenous NLRP3-ASC interaction but did not affect the NLRP3-NEK7 interaction, raising the possibility that it targets NLRP3 directly.

Synonyms: MK-341; SB 252218; N-5'

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Kim, Jaejeong ; Kang, Changyu ; Yoo, Jin-Wook ; Yoon, In-Soo ; Jung, Yunjin ;

Abstract: The selective agonist of β2-adrenergic receptor mirabegron (MBG), clinically used to treat overactive bladders, exerts beneficial effects in animal models of colitis. Here, we aimed to enhance the therapeutic activity and safety of MBG as an anticolitic drug by implementing colon-targeted drug delivery using a prodrug approach. MBG was azo-linked with salicylic acid (SA) to yield SA-conjugated MBG (MAS), which was conjugated with (Asp) and glutamic acid (Glu) to yield more hydrophilic derivatives: Asp-conjugated MAS (MAS-Asp) and Glu-conjugated MAS (MAS-Glu). MBG derivatives reduced the distribution coefficient and cell permeability of MBG, which were greater with the amino acid-conjugated MAS than with MAS. MBG derivatives were cleaved to release MBG in the cecal contents. Upon oral gavage, compared with MBG, MBG derivatives delivered greater amounts of MBG to the cecum while limiting the systemic absorption of MBG, and the amino acid-conjugated MAS exhibited a greater performance than MAS. In a rat colitis model, MBG derivatives were more effective than MBG in ameliorating colonic damage and inflammation, and the amino acid-conjugated MAS was more potent than MAS. MAS-Glu was therapeutically superior to , a current drug to treat inflammatory bowel disease, against rat colitis. Moreover, MBG activated the anti-inflammatory nuclear factor erythroid 2-related factor 2 (Nrf2)-hemeoxygenase (HO)-1 pathway in inflamed colonic tissue, and the MAS-Glu-mediated amelioration of colitis was significantly compromised by an HO-1 inhibitor. Taken together, colon-targeted delivery of MBG may enhance the anticolitic activity, reduce the risk of systemic side effects of MBG, and elicit the therapeutic effects, at least partly by activating the Nrf2-HO-1 pathway.

Keywords: colon-targeted drug delivery ; prodrug ; mirabegron ; inflammatory bowel disease ; beta-3 adrenergic receptor ; nuclear factor erythroid 2-related factor 2

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Mansoor, Farheen ; Jabeen, Almas ; Shah, Syeda Farah ; Simjee, Shabana U. ; Bano, Samina ; Faizi, Shaheen

Abstract: Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex has an important role in immune system and its abnormal activation is associated with the pathogenesis of various inflammatory and auto-immune diseases. The study reveals the anti-inflammatory effects of 3,6-dihydroxyflavone (3,6-DHF). Here, we aimed to determine the inhibitory effects of 3,6-DHF on NLRP3 inflammasome and its associated components, thereby determining the signaling pathways involved in the inhibition. Reactive oxygen species (ROS) and nitric oxide (NO) were quantified by chemiluminescence and Griess methods, resp. Inflammatory cell model was induced in human leukemic monocytes (THP-1). mRNA levels were estimated through real-time RT-PCR, protein expressions were evaluated by protein slot blot and immunocytochem., MTT and alamar blue assays were employed for toxicity studies. The compound 3,6-DHF was found to be the potent inhibitor of NLRP3 inflammasome by targeting the mols. involve in its activation pathway. Anti-inflammatory effects were revealed by inhibition of ROS and NO, reduction in the transcription of caspase-1, ASC, IL-1β and TLR-4 was observed along with the marked inhibition of NLRP3, IL-18, NF-κB and pNF-κB at translational level. 3,6-DHF was non-toxic on normal human fibroblast (BJ) and THP-1 cells and, could be a potential therapeutic agent in NLRP3 inflammasome driven diseases.

Keywords: Inflammation ; Autoimmune diseases ; NLRP3 inflammasome ; NOD-like receptor ; Pro-inflammatory cytokines ; Caspase-1

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Alternative Products

Product Details of Tranilast

CAS No. :53902-12-8
Formula : C18H17NO5
M.W : 327.33
SMILES Code : O=C(O)C1=CC=CC=C1NC(/C=C/C2=CC=C(OC)C(OC)=C2)=O
Synonyms :
MK-341; SB 252218; N-5'
MDL No. :MFCD00864787
InChI Key :NZHGWWWHIYHZNX-CSKARUKUSA-N
Pubchem ID :5282230

Safety of Tranilast

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of Tranilast

GPCR

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
THP-1 macrophages 100 µM 30 minutes TR inhibited caspase-1 activation and IL-1β secretion EMBO Mol Med. 2018 Apr;10(4):e8689.
M2 macrophages 50 µM 24 hours Tranilast inhibited the migration ability of M2 macrophages Gastric Cancer. 2022 May;25(3):515-526.
BMDMs 100 µM 30 minutes TR inhibited LPS-induced pro-IL-1β expression and IL-6 production, but had minimal effects on NLRP3 expression and TNF-α production EMBO Mol Med. 2018 Apr;10(4):e8689.
Leiomyoma smooth muscle cells (LSMC) 200 µM 48 hours Tranilast significantly increased the expression of miR-200c, and the effect was further enhanced when combined with Bay 117082 (an inhibitor of IκB phosphorylation). Fertil Steril. 2020 Jun;113(6):1308-1318.
Myometrium smooth muscle cells (MSMC) 200 µM 48 hours Tranilast significantly increased the expression of miR-200c, but the effect was more profound in LSMC compared to MSMC. Fertil Steril. 2020 Jun;113(6):1308-1318.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6 mice Gouty arthritis model Oral 200 mg/kg Once daily for 6 weeks TR can prevent NLRP3-dependent acute inflammation and tissue damage EMBO Mol Med. 2018 Apr;10(4):e8689.
C57BL/6J mice Peritoneal metastasis model Oral 200 mg/kg/day Daily for 14 days Tranilast inhibited tumor growth and fibrosis, reduced infiltration of M2 macrophages and mast cells, and significantly promoted CD8+ lymphocyte infiltration, leading to cancer cell apoptosis Gastric Cancer. 2022 May;25(3):515-526.
Mice SCID/Beige mouse model Intraperitoneal injection 50 mg/kg/day Daily for 8 weeks Tranilast showed therapeutic effects on fibroids in the mouse model, with a 37% reduction in tumor weight, significant decrease in staining for Ki67, CCND1, and E2F1, and a significant increase in nuclear staining for cleaved caspase 3. Int J Mol Sci. 2023 Jun 21;24(13):10465
Sprague Dawley rats Neuropathic pain model Intraperitoneal injection 50-200 mg/kg Single injection, lasting 48 hours To evaluate the analgesic effect of Tranilast on neuropathic pain, results showed that Tranilast significantly increased the pain threshold, with effects lasting up to 24 hours at doses of 100 and 200 mg/kg Int J Mol Sci. 2022 May 24;23(11):5878

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00818805 Allergic Conjunctivitis Phase 4 Completed - -
NCT01109121 Moderate to Severe Gout ... More >> Hyperuricemia Less << Phase 2 Completed - -
NCT01052987 Gout Hyperuri... More >>cemia Less << Phase 2 Completed - United States, Hawaii ... More >> Nuon Investigative Site Honolulu, Hawaii, United States United States, Indiana Nuon Investigative Site Evansville, Indiana, United States United States, Texas Nuon Investigative Site Dallas, Texas, United States Less <<
NCT00995618 Gout Hyperuri... More >>cemia Less << Phase 2 Completed - United States, Hawaii ... More >> Nuon Investigative Site Honolulu, Hawaii, United States United States, Indiana Nuon Investigative Site Evansville, Indiana, United States United States, Texas Nuon Investigative Site Dallas, Texas, United States Less <<
NCT00882024 Active Rheumatoid Arthritis Phase 2 Completed - -
NCT00717808 Rheumatoid Arthritis Phase 1 Withdrawn(Due to unforeseen ci... More >>rcumstances this study will not now start.) Less << September 2009 -
NCT03528070 Sarcoidosis EARLY_PHASE1 UNKNOWN 2025-12-20 -
NCT00818805 - Completed - -
NCT01003613 Pterygium Phase 3 Completed - Brazil ... More >> Hospital de Base/FAMERP Sao Jose do Rio Preto, Sao Paulo, Brazil, 15090-000 Less <<
NCT03490708 Mucinoses EARLY_PHASE1 UNKNOWN 2025-12-22 -
NCT03512873 Scleredema Adultorum EARLY_PHASE1 UNKNOWN 2025-12-20 -
NCT05626829 Nasopharyngeal Carcinoma|Recur... More >>rent Cancer Less << PHASE2 RECRUITING 2024-11-30 Southern medical university, G... More >>uangzhou, Guangdong, 510515, China Less <<
NCT03923140 Cryopyrin-Associated Periodic ... More >>Syndromes Less << PHASE2 UNKNOWN 2025-10-24 Peking Union Medical College H... More >>ospital, Beijing, Beijing, 100730, China Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.06mL

0.61mL

0.31mL

15.28mL

3.06mL

1.53mL

30.55mL

6.11mL

3.06mL

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