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| Targets |
Nicotinamide mononucleotide adenylyltransferase (NMNAT). NMNH is a reduced form of nicotinamide mononucleotide (NMN) that acts as a potent NAD⁺ enhancer, with its conversion to NAD(H) primarily mediated by NMNAT. [1]
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| ln Vitro |
NMNH treatment (100 μM) increased cellular NAD⁺ levels by approximately 5-fold in HepG2 cells after 12 hours, whereas NMN at the same concentration only slightly elevated NAD⁺ levels. NMNH also increased NAD⁺ in ES-2 cells (human ovary-derived) and 3T3-L1 cells (mouse embryo fibroblast-derived) in a time- and concentration-dependent manner. [1]
NMNH increased cellular NADH levels by approximately 2.5-fold in HepG2 cells compared to untreated controls after 12 hours of 100 μM treatment. [1] Metabolomic analysis revealed that NMNH decreased levels of glycolysis intermediates, including fructose-1,6-diphosphate, DHAP, 3PG/2PG, PEP, and pyruvate, as well as TCA cycle intermediates, including citrate, cis-aconitate, isocitrate, succinate, and malate. [1] Isotope tracing with ¹³C₆-glucose demonstrated that NMNH significantly suppressed glycolysis and the TCA cycle. [1] NMNH inhibited cell growth in HepG2 cells at concentrations >250 μM. At 500 μM, NMNH completely blocked growth of 786-O cells (clear cell renal cell carcinoma line). 786-O cells showed sensitivity to NMNH at concentrations as low as 50 μM, whereas HK-2 cells (normal kidney epithelial cells) required 250 μM for effective growth inhibition. [1] NMNH treatment (1 mM for 12 hours) induced cell cycle arrest in HepG2 cells, as determined by flow cytometry, while NMN had no effect on cell cycle. Proteomic analysis identified 289 up-regulated and 171 down-regulated proteins, with CDK1 being down-regulated. [1] NMNH treatment increased cellular nicotinamide (NAM) and NMN levels. [1] Knockdown of NMNAT1 using shRNA compromised the NAD⁺-enhancing effect of NMNH, confirming the role of NMNAT in NMNH-mediated NAD⁺ synthesis. [1] |
| ln Vivo |
In C57BL/6J male mice, intraperitoneal injection of NMNH (340 mg/kg) increased liver NAD⁺ levels by approximately 4-fold compared to PBS-treated controls, and 1.5-fold higher than NMN-treated mice. Oral administration also increased liver NAD⁺ by nearly 4-fold. [1]
NMNH treatment (340 mg/kg, i.p.) increased liver NADH levels by approximately 3-fold compared to PBS controls, and 1.7-fold higher than NMN-treated mice. [1] Long-term administration of NMNH (13.6 mg/kg, i.p., daily for 4 weeks) showed no difference in body weight curves among PBS-treated, NMNH-treated, and NMN-treated mice. [1] NMNH treatment increased mouse liver NAD⁺ and NADH contents in a dose-dependent manner, with 1000 mg/kg NMNH increasing liver NAD⁺ by over 10-fold and NADH by nearly 10-fold. [1] |
| Enzyme Assay |
No direct enzyme activity assay data (e.g., IC₅₀, Kᵢ) for NMNH are described in this article. However, the role of NMNAT in NMNH metabolism was confirmed using the NMNAT inhibitor tannic acid (which abolished the NAD⁺-increasing effect) and NMNAT1 knockdown. [1]
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| Cell Assay |
No direct enzyme activity assay data (e.g., IC₅₀, Kᵢ) for NMNH are described in this article. However, the role of NMNAT in NMNH metabolism was confirmed using the NMNAT inhibitor tannic acid (which abolished the NAD⁺-increasing effect) and NMNAT1 knockdown. [1]
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| Animal Protocol |
Mouse Dosing: Eight-week-old male C57BL/6J mice (weight 25±3 g) were randomly divided into PBS-treated, NMNH-treated, and NMN-treated groups. For acute studies, mice received intraperitoneal injection of 340 mg/kg NMNH or NMN, and were sacrificed 6 hours later for liver collection. For oral administration, NMNH was given via oral gavage. For dose-response studies, NMNH was administered at 50, 100, 500, or 1000 mg/kg via intraperitoneal injection every other day for one week. For long-term safety, mice received 13.6 mg/kg NMNH or NMN daily via intraperitoneal injection for 4 weeks. [1]
Blood Collection and Analysis: Sera were obtained by retro-orbital blood collection. Serum ALT and AST levels were measured using an automatic biochemical analyzer. [1] |
| ADME/Pharmacokinetics |
Mouse Dosing: Eight-week-old male C57BL/6J mice (weight 25±3 g) were randomly divided into PBS-treated, NMNH-treated, and NMN-treated groups. For acute studies, mice received intraperitoneal injection of 340 mg/kg NMNH or NMN, and were sacrificed 6 hours later for liver collection. For oral administration, NMNH was given via oral gavage. For dose-response studies, NMNH was administered at 50, 100, 500, or 1000 mg/kg via intraperitoneal injection every other day for one week. For long-term safety, mice received 13.6 mg/kg NMNH or NMN daily via intraperitoneal injection for 4 weeks. [1]
Blood Collection and Analysis: Sera were obtained by retro-orbital blood collection. Serum ALT and AST levels were measured using an automatic biochemical analyzer. [1] |
| Toxicity/Toxicokinetics |
NMNH was safe in mice with no observable difference in body weight after 4 weeks of daily dosing at 13.6 mg/kg. [1]
High-dose NMNH administration (50, 100, 500, or 1000 mg/kg every other day for one week) did not elevate serum ALT or AST levels, indicating no liver toxicity. [1] |
| References | |
| Additional Infomation |
NMNH (reduced nicotinamide mononucleotide) is the reduced form of nicotinamide mononucleotide (NMN). It was synthesized by reducing NMN with TDO (1,1,1-trifluoro-3-(4-iodophenyl)prop-1-en-2-ol) under alkaline conditions at 40°C for 1 hour. NMNH can also be generated enzymatically by degrading NADH with NudC (NADH pyrophosphatase). [1]
NMNH exhibits a characteristic UV absorption peak at 340 nm, distinguishing it from NMN (260 nm). [1] The mechanism of NAD⁺ enhancement by NMNH involves direct conversion to NADH via NMNAT, and potentially conversion to NMN (which is then converted to NAD⁺). NMNH treatment inhibits endogenous NAD⁺ synthesis via the NAMPT pathway. [1] Unlike NMN, NMNH significantly increases cellular NADH levels and suppresses glycolysis, the TCA cycle, and cell growth. These findings suggest that NMNH may have distinct biological effects compared to oxidized NAD⁺ precursors. [1] |
| Molecular Formula |
C11H15N2NA2O8P
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|---|---|
| Molecular Weight |
380.20
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| Exact Mass |
380.036141
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| CAS # |
108347-85-9
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| PubChem CID |
168490246
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
533
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| Defined Atom Stereocenter Count |
4
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| SMILES |
O[C@@H]1[C@@H]([C@@H](COP(O)(O)=O)O[C@H]1N1C=CCC(C(=O)N)=C1)O.[NaH]
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| InChi Key |
VBSHHBISJKQWQV-BXMOOSBBSA-L
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| InChi Code |
InChI=1S/C11H17N2O8P.2Na/c12-10(16)6-2-1-3-13(4-6)11-9(15)8(14)7(21-11)5-20-22(17,18)19;;/h1,3-4,7-9,11,14-15H,2,5H2,(H2,12,16)(H2,17,18,19);;/q;2*+1/p-2/t7-,8-,9-,11-;;/m1../s1
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| Chemical Name |
disodium;[(2R,3S,4R,5R)-5-(3-carbamoyl-4H-pyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate
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| Synonyms |
NMNH, reduced form disodium; Sodium ((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1(4H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate; 108347-85-9; G63019
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
H2O : ~125 mg/mL (~328.77 mM; with ultrasonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6302 mL | 13.1510 mL | 26.3019 mL | |
| 5 mM | 0.5260 mL | 2.6302 mL | 5.2604 mL | |
| 10 mM | 0.2630 mL | 1.3151 mL | 2.6302 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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