| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
|
||
| 500mg |
|
||
| 5g |
|
||
| Other Sizes |
| Targets |
1. CXC chemokine receptor 2 (CXCR2, for the 3-substituted nicotinamide N-oxide derivative, IC50=1.5 μM in binding assay)[2]
2. Cytochrome P450 2E1 (CYP2E1, responsible for the formation of Nicotinamide N-oxide from nicotinamide)[1] |
|---|---|
| ln Vitro |
Niacinamide is a type of vitamin B3. It is a precursor of nicotinamide adenine dinucleotide, which is well recognized as an electron transporter in oxidative phosphorylation and a cofactor for numerous dehydrogenases. It is metabolized by two enzyme systems. The first system begins with methylation of nicotinamide by nicotinamide N-methyltransferase, which can then be oxidized by aldehyde oxidase. The second enzyme system oxidizes nicotinamide to nicotinamide N-oxide [1]. A series of nicotinamide N-oxides were produced and proved to be novel, powerful and specific antagonists of the CXCR2 receptor. Compound 1 has been proven to efficiently block neutrophil chemotaxis (IC50=10 nM). Compound 2 is a selective antagonist of IL-8 binding (IC50=110 nM) and a powerful inhibitor of neutrophil chemotaxis (IC50=170 nM) [2].
1. In human liver microsome incubation systems: The formation of Nicotinamide N-oxide from nicotinamide was predominantly catalyzed by CYP2E1; the reaction was inhibited by specific CYP2E1 inhibitors (e.g., 4-methylpyrazole) in a concentration-dependent manner, while inhibitors of other CYP isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) showed no significant inhibitory effect on the formation of Nicotinamide N-oxide; recombinant CYP2E1 enzyme could efficiently catalyze the N-oxidation of nicotinamide to produce Nicotinamide N-oxide with clear enzyme kinetic characteristics[1] 2. In CXCR2 receptor activity assays: 3-substituted nicotinamide N-oxide derivatives exhibited potent antagonistic activity against CXCR2; the lead compound (3-amino-6-chloronicotinamide N-oxide) showed an IC50 of 1.5 μM in CXCR2 binding assay and effectively inhibited CXCL8-induced calcium mobilization in CXCR2-expressing cells with IC50 of 2.2 μM, while the unsubstituted Nicotinamide N-oxide had weaker CXCR2 antagonistic activity[2] |
| Enzyme Assay |
1. CYP2E1-mediated nicotinamide N-oxidation assay: Prepare incubation mixtures containing human liver microsomes or recombinant CYP2E1 enzyme, nicotinamide substrate, NADPH-regenerating system, and different concentrations of CYP isozyme-specific inhibitors; incubate the mixtures at 37℃ for 10-60 min; terminate the reaction by adding ice-cold acetonitrile; centrifuge the mixture to remove proteins; separate and quantify Nicotinamide N-oxide and unmetabolized nicotinamide using high-performance liquid chromatography with ultraviolet detection; calculate enzyme activity, inhibition rate and kinetic parameters (Km and Vmax) of the reaction[1]
2. CXCR2 receptor binding assay: Prepare membrane fractions from CXCR2-overexpressing cells; incubate the membrane preparations with radiolabeled CXCL8 ligand, different concentrations of Nicotinamide N-oxide or its derivatives, and buffer components at room temperature for 1 h; separate bound and free ligands by rapid filtration through glass fiber filters; wash the filters and determine radioactivity using a scintillation counter; calculate the IC50 values for competitive binding to CXCR2[2] |
| ADME/Pharmacokinetics |
1. In vitro metabolic source: Nicotinamide N-oxide is the main metabolite of nicotinamide in human liver microsomes, and its generation is entirely mediated by CYP2E1; the Km value of nicotinamide N-oxidation catalyzed by CYP2E1 is 125 μM, and the Vmax value is 1.2 nmol/min/mg protein [1].
|
| References | |
| Additional Infomation |
Nicotinamide N-oxide belongs to the pyridine class of compounds.
1. Nicotinamide N-oxide is an endogenous metabolite generated in the human liver from the N-oxidation reaction of nicotinamide catalyzed by CYP2E1, and can also be used as a scaffold for the chemical synthesis of CXCR2 antagonists[1][2]. 2. 3-substituted nicotinamide N-oxide derivatives have been designed as CXCR2 antagonists for the treatment of inflammatory diseases, as CXCR2 is a key mediator of neutrophil recruitment in acute and chronic inflammation[2]. 3. CYP2E1 is the only CYP isoenzyme in the human liver responsible for the N-oxidation of nicotinamide, which distinguishes this metabolic pathway from other nicotinamide oxidation reactions[1]. |
| Molecular Formula |
C6H6N2O2
|
|---|---|
| Molecular Weight |
138.1240
|
| Exact Mass |
138.043
|
| CAS # |
1986-81-8
|
| PubChem CID |
72661
|
| Appearance |
White to off-white solid powder
|
| Density |
1.34 g/cm3
|
| Boiling Point |
514.7ºC at 760 mmHg
|
| Melting Point |
291-293 °C (dec.)(lit.)
|
| Flash Point |
265.1ºC
|
| Vapour Pressure |
1.05E-10mmHg at 25°C
|
| Index of Refraction |
1.602
|
| LogP |
0.914
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
10
|
| Complexity |
138
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
USSFUVKEHXDAPM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C6H6N2O2/c7-6(9)5-2-1-3-8(10)4-5/h1-4H,(H2,7,9)
|
| Chemical Name |
1-oxidopyridin-1-ium-3-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
H2O : ~20 mg/mL (~144.80 mM)
DMSO : ~10 mg/mL (~72.40 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (7.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (7.24 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 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: 5.56 mg/mL (40.25 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 7.2401 mL | 36.2004 mL | 72.4008 mL | |
| 5 mM | 1.4480 mL | 7.2401 mL | 14.4802 mL | |
| 10 mM | 0.7240 mL | 3.6200 mL | 7.2401 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
