1. Metabolic Enzyme/Protease Apoptosis
  2. NADPH Oxidase Apoptosis Bcl-2 Family
  3. Dihydronicotinamide riboside

Dihydronicotinamide riboside is a potent NAD+ concentration enhancer. Dihydronicotinamide riboside modulates targets BAX, PUMA, NQO2, and IκB kinase. Dihydronicotinamide riboside mediates apoptosis, induces pro-oxidant activity, mitochondrial dysfunction, metabolic dysregulation, redox modulation, and pro-inflammatory M1 phenotype induction. Dihydronicotinamide riboside increases intracellular and mitochondrial NAD+ levels, maintains cell survival against NAD+-depleting genotoxins. Dihydronicotinamide riboside can be used for the research of hepatocellular carcinoma.

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Dihydronicotinamide riboside

Dihydronicotinamide riboside Chemical Structure

CAS No. : 19132-12-8

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Description

Dihydronicotinamide riboside is a potent NAD+ concentration enhancer. Dihydronicotinamide riboside modulates targets BAX, PUMA, NQO2, and IκB kinase. Dihydronicotinamide riboside mediates apoptosis, induces pro-oxidant activity, mitochondrial dysfunction, metabolic dysregulation, redox modulation, and pro-inflammatory M1 phenotype induction. Dihydronicotinamide riboside increases intracellular and mitochondrial NAD+ levels, maintains cell survival against NAD+-depleting genotoxins. Dihydronicotinamide riboside can be used for the research of hepatocellular carcinoma[1][2][3].

In Vitro

Dihydronicotinamide riboside (100-1000 μM; 24 h followed by 48 h in fresh medium) induces dose-dependent cytotoxicity in HepG3 cells but has no cytotoxic effect on HEK293T cells[1].
Dihydronicotinamide riboside (500 μM; 24 h with total incubation periods of 24, 48, 72 h) induces PUMA- and BAX-mediated apoptosis in HepG3 cells, with BAX expression peaking at 72 h and PUMA expression peaking at 72 h, while HEK293T cells show no significant changes in apoptotic marker expression[1].
Dihydronicotinamide riboside (100 μM; 1, 4, 24 h) induces a transient but significant increase in cellular ROS levels in HepG3 cells at 4 h, while HEK293T cells show no change in ROS levels over 1, 4, or 24 h of exposure[1].
Dihydronicotinamide riboside (100 μM; 1, 4, 24 h) increases intracellular NAD(P)H levels in both HEK293T and HepG3 cells, with HEK293T cells showing a progressive increase over 24 h and HepG3 cells showing a peak increase at 4 h followed by a slight decline[1].
Dihydronicotinamide riboside (100 μM; 1, 4, 24 h) alters the glutathione redox balance in HEK293T and HepG3 cells, causing a sustained decrease in GSSG levels in HEK293T cells and a transient decrease in GSSG levels in HepG3 cells at 4 h, with no significant changes in GSH levels in either cell line[1].
Dihydronicotinamide riboside (100 μM; 1, 4, 24 h) induces a significant and sustained increase in mitochondrial superoxide production in HepG3 cells, while HEK293T cells show no change in mitochondrial superoxide levels over the same exposure periods[1].
Dihydronicotinamide riboside (100-2000 μM; 1-18 h) potently increases NAD+ concentrations in multiple immortalized mammalian cell lines, with an EC50 of 310 μM in Neuro2a cells, achieving up to 10-fold elevation over control values after 6 h of treatment[2].
Dihydronicotinamide riboside (1 mM; 6 h) increases NAD+ concentrations in HAP1 cells independently of Nrk1, achieving a 6.8-fold elevation over control values after 6 h of treatment with 1 mM NRH in both wild-type and Nrk1 knockout cells[2].
Dihydronicotinamide riboside (NRH) (500 μM; 6 h) significantly boosts intracellular NAD+ levels in both undifferentiated and Phorbol 12-myristate 13-acetate (PMA) (HY-18739)-differentiated human THP-1 monocytic cells, with a stronger effect observed in undifferentiated cells[3].
Dihydronicotinamide riboside (NRH) (500 μM; 6 h) induces significant pro-inflammatory gene expression in PMA-differentiated human THP-1 macrophage-like cells[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay[1]

Cell Line: human embryonic kidney (HEK293T) cells, human hepatocellular carcinoma (HepG3) cells
Concentration: 100, 250, 500, 750, 1000 μM
Incubation Time: 24 h, followed by 48 h in fresh medium
Result: Induced 15%, 50%, 90% cytotoxicity in HepG3 cells at 100, 250, ≥500 μM, respectively.
Showed no cytotoxicity in HEK293T cells across all tested concentrations.

Western Blot Analysis[1]

Cell Line: human embryonic kidney (HEK293T) cells, human hepatocellular carcinoma (HepG3) cells
Concentration: 500 μM
Incubation Time: 24 h, with total incubation periods of 24, 48, 72 h
Result: Increased BAX expression by 40% at 24 h, 50% at 48 h, and 110% at 72 h in HepG3 cells relative to control.
Increased PUMA expression by 140% at 48 h and 150% at 72 h in HepG3 cells relative to control.
Showed no significant changes in BAX or PUMA expression in HEK293T cells at any time point.

Real Time qPCR[1]

Cell Line: human embryonic kidney (HEK293T) cells, human hepatocellular carcinoma (HepG3) cells
Concentration: 100 μM
Incubation Time: 1, 4, 24 h
Result: Induced a significant reduction in mtDNA amplification (indicating damage) by 57±7.7% at 1 h and 40% at 4 h in HepG3 cells, with recovery to near-control levels by 24 h.
Induced a significant 27% reduction in mtDNA amplification in HEK293T cells at 1 h, with no significant changes at 4 or 24 h.
In Vivo

Dihydronicotinamide riboside (250-1000 mg/kg; i.p.; single dose) administered as a single intraperitoneal dose increases tissue NAD+ concentrations in healthy male C57BL/6J mice, with a 5.4-fold increase in liver observed at both 1000 mg/kg and 250 mg/kg doses[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6J (male, 8 weeks old)[2]
Dosage: 1000 mg/kg; 250 mg/kg
Administration: i.p.; single dose
Result: Increased NAD+ concentrations 2.4-fold in blood, 5.4-fold in liver, 3.1-fold in kidney, 2.2-fold in brain, 1.2-fold in skeletal muscle, and 2.7-fold in epididymal adipose tissue at 1000 mg/kg.
Increased NAD+ concentrations 5.4-fold in liver and 1.8-fold in kidney at 250 mg/kg.
Molecular Weight

256.26

Formula

C11H16N2O5

CAS No.
Appearance

Solid

Color

Yellow to brown

SMILES

NC(C1=CN([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)C=CC1)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

-20°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

Solvent & Solubility
In Vitro: 

H2O : 100 mg/mL (390.23 mM; Need ultrasonic)

DMSO : 3.85 mg/mL (15.02 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.9023 mL 19.5114 mL 39.0229 mL
5 mM 0.7805 mL 3.9023 mL 7.8046 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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In Vivo Dissolution Calculator
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This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).
Purity & Documentation

Purity: 95.0%

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO / H2O 1 mM 3.9023 mL 19.5114 mL 39.0229 mL 97.5572 mL
5 mM 0.7805 mL 3.9023 mL 7.8046 mL 19.5114 mL
10 mM 0.3902 mL 1.9511 mL 3.9023 mL 9.7557 mL
15 mM 0.2602 mL 1.3008 mL 2.6015 mL 6.5038 mL
H2O 20 mM 0.1951 mL 0.9756 mL 1.9511 mL 4.8779 mL
25 mM 0.1561 mL 0.7805 mL 1.5609 mL 3.9023 mL
30 mM 0.1301 mL 0.6504 mL 1.3008 mL 3.2519 mL
40 mM 0.0976 mL 0.4878 mL 0.9756 mL 2.4389 mL
50 mM 0.0780 mL 0.3902 mL 0.7805 mL 1.9511 mL
60 mM 0.0650 mL 0.3252 mL 0.6504 mL 1.6260 mL
80 mM 0.0488 mL 0.2439 mL 0.4878 mL 1.2195 mL
100 mM 0.0390 mL 0.1951 mL 0.3902 mL 0.9756 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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Dihydronicotinamide riboside
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