Novel role for tranilast in regulating NLRP3 ubiquitination, vascular inflammation, and atherosclerosis was written by Chen, Suwen;Wang, Yadong;Pan, Yamu;Liu, Yao;Zheng, Shuang;Ding, Ke;Mu, Kaiyu;Yuan, Ye;Li, Zhaoyang;Song, Hongxian;Jin, Ying;Fu, Jian. And the article was included in Journal of the American Heart Association in 2020.Safety of 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid This article mentions the following:
Aberrant activation of the NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat-containing receptor family pyrin domain-containing 3) inflammasome is thought to play a causative role in atherosclerosis. NLRP3 is kept in an inactive ubiquitinated state to avoid unwanted NLRP3 inflammasome activation. This study aimed to test the hypothesis that pharmacol. manipulating of NLRP3 ubiquitination blunts the assembly and activation of the NLRP3 inflammasome and protects against vascular inflammation and atherosclerosis. Since genetic studies yielded mixed results about the role for this inflammasome in atherosclerosis in low-d. lipoprotein receptor- or apolipoprotein E-deficient mice, this study attempted to clarify the discrepancy with the pharmacol. approach using both models. We provided the first evidence demonstrating that tranilast facilitates NLRP3 ubiquitination. We showed that tranilast restricted NLRP3 oligomerization and inhibited NLRP3 inflammasome assembly. Tranilast markedly suppressed NLRP3 inflammasome activation in low-d. lipoprotein receptor- and apolipoprotein E-deficient macrophages. Through reconstitution of the NLRP3 inflammasome in human embryonic kidney 293T cells, we found that tranilast directly limited NLRP3 inflammasome activation. By adopting different regimens for tranilast treatment of low-d. lipoprotein receptor- and apolipoprotein E-deficient mice, we demonstrated that tranilast blunted the initiation and progression of atherosclerosis. Mice receiving tranilast displayed a significant reduction in atherosclerotic lesion size, concomitant with a pronounced decline in macrophage content and expression of inflammatory mols. in the plaques compared with the control group. Moreover, tranilast treatment of mice substantially hindered the expression and activation of the NLRP3 inflammasome in the atherosclerotic lesions. Tranilast potently enhances NLRP3 ubiquitination, blunts the assembly and activation of the NLRP3 inflammasome, and ameliorates vascular inflammation and atherosclerosis in both low-d. lipoprotein receptor- and apolipoprotein E-deficient mice. In the experiment, the researchers used many compounds, for example, 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8Safety of 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid).
2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8) belongs to amides. The solubilities of amides and esters are roughly comparable. Typically amides are less soluble than comparable amines and carboxylic acids since these compounds can both donate and accept hydrogen bonds. Tertiary amides, with the important exception of N,N-dimethylformamide, exhibit low solubility in water. As a result of interactions such as these, the water solubility of amides is greater than that of corresponding hydrocarbons. These hydrogen bonds are also have an important role in the secondary structure of proteins.Safety of 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid
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Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics