TRIA-662 (1-Methylnicotinamide chloride) is the principal metabolite of nicotinamide generated by nicotinamide N-methyltransferase (NNMT)[1]. TRIA-662 exerts antithrombotic and anti-inflammatory effects by promoting prostacyclin release and improving nitric-oxide bioavailability[2]. TRIA-662 is commonly used as a fluorogenic probe substrate as well as food supplement ingredient[3][4].
In vitro, treatment of human dermal microvascular endothelial cells (HMECs) with TRIA-662(0.1μM; 3h) reduced TNF-α-induced increases in endothelial cell stiffness, induced slight F-actin depolymerization, and restored NO and PGI₂ levels toward baseline[5].
In vivo, TRIA-662 (100mg/kg/day; p.o.; 19 days)showed significant anti-metastasis activity, increased tumor angiogenesis,decreased the number of lung metastases and elevated the E-cadherin to N-cadherin expression ratio in the 4T1 tumor-bearing mouse model[6]. TRIA-662 (200µL;300mM; i.v.; 10min before hypoxic stress) reduced the hypoxia-induced cardiac injury biomarker troponin T levels, decreased creatine kinase activity, and increased myocardial phosphocreatine content and phosphocreatine/creatine ratio in ApoE-/-LDLr-/- mice without causing hypernatremia[7].
References:
[1] Wozniacka A, Wieczorkowska M, Gebicki J, Sysa-Jedrzejowska A. Topical application of 1-methylnicotinamide in the treatment of rosacea: a pilot study. Clin Exp Dermatol. 2005;30(6):632-635.
[2] Szafarz M, Kus K, Walczak M, et al. Pharmacokinetic Profile of 1-Methylnicotinamide Nitrate in Rats. J Pharm Sci. 2017;106(5):1412-1418.
[3] Elokely KM, Eldawy MA, Elkersh MA, El-Moselhy TF. Fluorescence Spectrometric Determination of Drugs Containing α-Methylene Sulfone/Sulfonamide Functional Groups Using N-Methylnicotinamide Chloride as a Fluorogenic Agent. Int J Anal Chem. 2011;2011:840178.
[4] EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), Turck D, Bresson JL, et al. Safety of 1-methylnicotinamide chloride (1-MNA) as a novel food pursuant to Regulation (EC) No 258/97. EFSA J. 2017;15(10):e05001.
[5] Kolodziejczyk AM, Brzezinka GD, Khurana K, Targosz-Korecka M, Szymonski M. Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride. Int J Nanomedicine. 2013;8:2757-2767.
[6] Blazejczyk A, Switalska M, Chlopicki S, et al. 1-methylnicotinamide and its structural analog 1,4-dimethylpyridine for the prevention of cancer metastasis. J Exp Clin Cancer Res. 2016;35(1):110.
[7] Zabielska MA, Adamus J, Kowalski R, et al. Cardioprotective effect of N-methylnicotinamide salt of pyruvate in experimental model of cardiac hypoxia. Pharmacol Rep. 2018;70(2):378-384.
TRIA-662 (1-Methylnicotinamide chloride)是烟酰胺经烟酰胺N-甲基转移酶（NNMT）催化生成的主要代谢产物[1]。TRIA-662通过促进前列环素释放及改善一氧化氮生物利用度，具有抗血栓和抗炎作用[2]。TRIA-662常用作荧光探针底物以及食品补充剂成分[3][4]。
在体外实验中，以0.1µM浓度处理人微血管内皮细胞（HMECs）3小时，TRIA-662显著降低了TNF-α诱导的细胞弹性增加，诱导F-肌动蛋白轻微解聚，并使NO和PGI₂水平恢复至接近正常水平[5]。
在体内实验中，TRIA-662（100mg/kg/天；口服；19天）在4T1肿瘤小鼠模型中显示出显著的抗转移活性，增加了肿瘤血管生成，减少了肺部转移灶数量，并提高了E-钙粘蛋白与N-钙粘蛋白的表达比值[6]。TRIA-662（200µL；300mM；静脉注射；缺氧应激前10分钟）降低ApoE-/-LDLr-/-小鼠缺氧诱导的心脏损伤生物标志物肌钙蛋白T水平，降低肌酸激酶活性，增加心肌磷酸肌酸含量和磷酸肌酸/肌酸比值，而不引起高钠血症[7]。