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Chemical Structure| 53902-12-8 Chemical Structure| 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 aspartic acid (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 sulfasalazine, 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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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
 

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