| Size | Price | Stock | Qty |
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| 250mg |
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| 1g |
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| Targets |
TRIA-662 iodide targets multiple pathways related to inflammation and thrombosis. The active moiety (1-methylnicotinamide, 1-MNA) exerts its antithrombotic effects by inhibiting platelet aggregation and activation. The proposed molecular mechanism involves activation of the prostacyclin (PGI2) pathway: 1-MNA stimulates the release of prostacyclin (PGI2) from vascular endothelial cells, which in turn activates the prostacyclin receptor (IP receptor) on platelets, leading to increased cAMP levels and reduced platelet reactivity. 1-MNA also exhibits anti-inflammatory activity by downregulating the expression of pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1beta) and adhesion molecules (VCAM-1, ICAM-1) in endothelial cells, possibly through inhibition of NF-kappaB signaling. Additionally, 1-MNA may act as a substrate for NNMT, modulating nicotinamide metabolism and NAD+ levels, though this is not considered its primary mechanism for antithrombotic effects. Thus, the targets include the prostacyclin pathway, platelet IP receptors, and components of the inflammatory signaling cascade.
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| ln Vitro |
In vitro, TRIA-662 (as the chloride or iodide salt) exhibits concentration-dependent inhibition of platelet aggregation. In human platelet-rich plasma, TRIA-662 at concentrations of 10-100 microM significantly reduces aggregation induced by ADP (20 microM), collagen (2 microg/mL), or thrombin (1 U/mL), with IC50 values typically 30-50 microM. The anti-aggregatory effect is mediated by increased intraplatelet cAMP levels, which can be measured by ELISA. TRIA-662 also inhibits the release of ATP and serotonin from activated platelets. In endothelial cell cultures (e.g., HUVEC), TRIA-662 (1-100 microM) stimulates the production of prostacyclin (PGI2, measured as its stable metabolite 6-keto-PGF1alpha) in a time- and concentration-dependent manner, with maximal effect observed at 50-100 microM. This effect is cyclooxygenase-dependent and can be blocked by indomethacin. In monocyte/macrophage cell lines (e.g., RAW264.7), TRIA-662 (10-100 microM) reduces LPS-induced production of TNF-alpha, IL-6, and nitric oxide (NO) by 30-50% without causing cytotoxicity. These in vitro activities are salt-independent; the iodide salt is expected to have identical activity to the chloride salt on a molar basis, assuming complete dissociation in aqueous medium.
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| ln Vivo |
In vivo, TRIA-662 (1-methylnicotinamide) has been studied in various rodent models of thrombosis and inflammation. In a mouse model of carotid artery thrombosis (induced by FeCl3 injury), intravenous administration of TRIA-662 chloride (10-50 mg/kg) significantly prolongs occlusion time (time to thrombotic vessel occlusion) and reduces thrombus weight in a dose-dependent manner. Oral administration of TRIA-662 (30-100 mg/kg) also reduces thrombus formation in rat models of venous thrombosis (stasis-induced). In a rat model of LPS-induced systemic inflammation, TRIA-662 (30 mg/kg, IP) reduces plasma levels of TNF-alpha and IL-6 by approximately 40-60% and attenuates leukocyte adhesion to the endothelium. In a mouse model of colitis (DSS-induced), TRIA-662 treatment (50 mg/kg/day, oral) reduces disease activity index (DAI), colon shortening, and histological damage. The iodide salt (CAS 6456-44-6) is less commonly used in vivo than the chloride form, but is expected to have equivalent efficacy if adjusted for molar concentration. No direct comparison studies between the two salts are available.
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| Enzyme Assay |
General protocol for in vitro enzyme/receptor binding (non-cellular): For assessing prostacyclin (PGI2) release from endothelial cells, an ELISA-based method is used. Culture HUVECs (human umbilical vein endothelial cells) in 24-well plates to confluence (1×10^5 cells/well). Replace medium with fresh phenol red-free DMEM containing 0.1% BSA. Add varying concentrations of TRIA-662 iodide (1, 10, 50, 100, 500 microM; dissolved in water or PBS) to wells. Include control wells (buffer) and positive control (histamine 10 microM or calcium ionophore A23187 1 microM). Incubate at 37degC for 30-60 minutes. Collect supernatants, centrifuge to remove cells, and measure 6-keto-PGF1alpha (the stable hydrolysis product of PGI2) using a commercial ELISA kit (detection range 10-5000 pg/mL). For platelet aggregation inhibition, use a platelet aggregometer. Collect human blood into 3.8% sodium citrate (9:1). Centrifuge at 200×g for 10 min to obtain platelet-rich plasma (PRP). Dilute TRIA-662 iodide in PBS to final concentrations of 1-500 microM. Pre-incubate PRP (250 microL) with compound for 2 min at 37degC in the aggregometer cuvette. Add agonist (ADP, collagen, or thrombin) and measure light transmission for 5-10 min. Record maximum aggregation percentage and calculate IC50 from dose-response curves. For cAMP measurement, incubate PRP with compound, then add IBMX (100 microM, a phosphodiesterase inhibitor) and extract with perchloric acid; measure cAMP by competitive ELISA.
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| Cell Assay |
General protocol for in vitro cell-based experiments: For anti-inflammatory activity, culture RAW264.7 mouse macrophages in DMEM with 10% FBS. Seed in 96-well plates at 2×10^5 cells/well and incubate overnight. Pre-treat cells with TRIA-662 iodide (10, 25, 50, 100 microM in culture medium, final DMSO ≤0.1%) for 2 hours. Then add lipopolysaccharide (LPS, 1 microg/mL) and continue incubation for 24 hours. Collect supernatants and measure TNF-alpha and IL-6 using ELISA kits. For NO measurement, add 100 microL of Griess reagent (1% sulfanilamide, 0.1% napthylethylenediamine dihydrochloride in 2.5% H3PO4) to 100 microL supernatant, incubate 10 min, and read OD540. Evaluate cytotoxicity using MTT assay in parallel wells (treat cells with compound but no LPS). For endothelial cell activation studies, culture HUVECs in 6-well plates, treat with TRIA-662 iodide (10-100 microM) for 24 hours, then stimulate with TNF-alpha (10 ng/mL) for 6 hours. Harvest cells and isolate RNA, perform qRT-PCR for VCAM-1, ICAM-1, and E-selectin mRNA expression. Alternatively, quantify surface adhesion molecule expression by flow cytometry using specific antibodies. TRIA-662 should reduce TNF-alpha-induced adhesion molecule upregulation by 30-60%.
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| Animal Protocol |
General protocol for in vivo animal experiments: For thrombosis model, use male C57BL/6 mice (8-10 weeks, 20-25 g). Anesthetize mice with ketamine/xylazine (100/10 mg/kg, IP). Expose the carotid artery and place a Doppler flow probe around it. Induce thrombosis by applying a strip of filter paper soaked in 10% FeCl3 to the adventitial surface of the artery for 3 minutes. Administer TRIA-662 iodide (10, 30, or 100 micromol/kg, adjusted for iodide salt molecular weight) or vehicle (saline) intravenously (tail vein) 10 minutes before FeCl3 application. Alternatively, administer orally by gavage 1 hour before. Record the time from FeCl3 application to complete cessation of blood flow (occlusion time) for up to 60 minutes. An occlusion time >60 minutes indicates complete protection. For statistical analysis, occlusion times are compared using log-rank (Kaplan-Meier) test. For anti-inflammatory activity, use a LPS-induced systemic inflammation model: inject C57BL/6 mice with LPS (10 mg/kg, IP) to induce sepsis-like condition. Administer TRIA-662 iodide (30 mg/kg, IP) 1 hour before and 1 hour after LPS challenge. Collect blood 6 hours post-LPS, separate serum, and measure TNF-alpha, IL-6, and IL-1beta by ELISA. Collect lungs for histology (H&E) and MPO (myeloperoxidase) assay to assess neutrophil infiltration. TRIA-662 should significantly reduce serum cytokines and lung inflammation.
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| ADME/Pharmacokinetics |
General pharmacokinetic properties: TRIA-662 (1-methylnicotinamide) is an endogenous metabolite, so its pharmacokinetics are influenced by its biosynthesis and clearance pathways. In humans, plasma levels of 1-MNA under normal conditions are approximately 0.1-1 microM. After oral administration of TRIA-662 chloride (500 mg, equivalent to niacin supplementation), Cmax reaches 20-50 microM within 1-2 hours. The plasma half-life (t1/2) is approximately 2-4 hours. Volume of distribution (Vd) is large (>1 L/kg), suggesting extensive tissue distribution. Protein binding is low (<10%). The compound is primarily cleared by renal excretion as unchanged drug, accounting for 60-80% of elimination. Minor metabolism includes further methylation and oxidation to other pyridine derivatives. In rodents, oral bioavailability of TRIA-662 is moderate (30-50%). The iodide salt (MW 264) has a lower molar concentration per unit weight compared to the chloride salt (MW 172.6); thus, dosing should be adjusted based on molar equivalents of the 1-MNA cation. TRIA-662 crosses the blood-brain barrier to a limited extent. The compound is stable in plasma for hours at room temperature; however, for accurate quantification in biological samples, use LC-MS/MS with a stable isotope internal standard (e.g., TRIA-662-d3).
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| Toxicity/Toxicokinetics |
General toxicity profile: TRIA-662 (1-methylnicotinamide) is an endogenous metabolite of nicotinamide with a good safety profile. In acute toxicity studies in rodents, the oral LD50 of TRIA-662 chloride is >2000 mg/kg, and no observable adverse effects are reported at doses up to 500 mg/kg. In subchronic studies (28-day oral, rats), doses up to 200 mg/kg/day do not cause changes in body weight, organ weights, blood chemistry, or histopathology of major organs. TRIA-662 iodide is expected to have a similar safety profile, but the iodide counterion may contribute additional toxicity at very high doses (iodide toxicity, including iodism, at doses >1 mg/kg/day in humans). However, at the concentrations used in research (usually <100 mg/kg for in vivo studies), iodide levels are below known toxic thresholds. In vitro, TRIA-662 shows no genotoxicity in the Ames test (up to 5000 microg/plate) and no clastogenic activity in the micronucleus assay. No reproductive toxicity data are available specifically for TRIA-662. However, as a vitamin B3 metabolite, it is considered safe at normal physiological levels. TRIA-662 is not a controlled substance. Standard laboratory safety precautions apply.
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| References | |
| Additional Infomation |
TRIA-662 iodide (CAS 6456-44-6) is also known as 1-methylnicotinamide iodide or 1-MNA iodide. The compound is the iodide salt of the quaternary ammonium cation 1-methylnicotinamide, which is a structural analog of the more common cofactor NAD+. TRIA-662 is metabolically stable in plasma but can be degraded by certain bacteria in the gut. The compound is soluble in water and ethanol. Store lyophilized powder at -20degC, protected from light, desiccated. Aqueous solutions are stable at 4degC for up to 1 week. The biological activity of TRIA-662 was first studied in the 1990s for its antithrombotic effects, and subsequent research has explored its potential as a therapeutic for cardiovascular diseases, including myocardial infarction and stroke. Compared to niacin (nicotinic acid), which causes uncomfortable flushing due to prostaglandin D2 release, TRIA-662 does not cause flushing, making it a potential alternative. However, it has not yet received regulatory approval as a drug; it remains a research compound. The iodide salt form is less commonly used than the chloride salt due to cost and availability. For in vivo experiments, the chloride salt is preferred because it avoids iodide-related toxicities at high doses. Use of TRIA-662 iodide should be justified when studying counterion effects.
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| Molecular Formula |
C7H9IN2O
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| Molecular Weight |
264.06
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| Exact Mass |
263.976
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| CAS # |
6456-44-6
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| Related CAS # |
TRIA-662-d3; 1-Methylnicotinamide-13C,d3 iodide; 3-Carbamoyl-1-methylpyridin-1-ium-d3 iodide; TRIA-662; 1-Methylnicotinamide-d4 iodide
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| PubChem CID |
72660
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
11
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| Complexity |
136
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C[N+]1=CC=CC(=C1)C(=O)N.[I-]
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| InChi Key |
IWEIZMCTGMHCRE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C7H8N2O.HI/c1-9-4-2-3-6(5-9)7(8)10;/h2-5H,1H3,(H-,8,10);1H
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| Chemical Name |
1-methylpyridin-1-ium-3-carboxamide iodide
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| Synonyms |
1-methylnicotinamide iodide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~66.67 mg/mL (~252.48 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (18.94 mM)(saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 50.0 mg/mL clear DMSO stock solution was added to 900 μL of 20% SBE-β-CD physiological saline solution and mixed thoroughly. 2 g of SBE-β-CD (sulfobutyl ether β-cyclodextrin) powder was diluted to 10 mL of physiological saline and dissolved completely until clear and transparent. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7870 mL | 18.9351 mL | 37.8702 mL | |
| 5 mM | 0.7574 mL | 3.7870 mL | 7.5740 mL | |
| 10 mM | 0.3787 mL | 1.8935 mL | 3.7870 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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