Endogenous Metabolite

Increasing evidence has indicated that NAD+ and NADH play critical roles not only in energy metabolism, but also in cell death and various cellular functions including regulation of calcium homeostasis and gene expression. It has also been indicated that NAD+ and NADH are mediators of multiple major biological processes including aging. NAD+ and NADH produce the biological effects by regulating numerous NAD+/NADH-dependent enzymes, including dehydrogenases, poly(ADP-ribose) polymerases, Sir2 family proteins (sirtuins), mono(ADP-ribosyl)transferases, and ADP-ribosyl cyclases. Of particular interest, NAD+-dependent generation of ADP-ribose, cyclic ADP-ribose and O-acetyl-ADP-ribose can mediate calcium homeostasis by affecting TRPM2 receptors and ryanodine receptors; and sirtuins and PARPs appear to play key roles in aging, cell death and a variety of cellular functions. It has also been indicated that NADH and NAD+ can be transported across plasma membranes of cells, and that extracellular NAD+ may be a new signaling molecule. Our latest studies have shown that intranasal NAD+ administration can profoundly decrease ischemic brain damage. These new pieces of information have fundamentally changed our understanding about NAD+ and NADH, suggesting novel paradigms about the metabolism and biological activities of NAD+ and NADH. Based on this information, it is tempted to hypothesize that NAD+ and NADH, together with ATP and Ca2+, may be four most fundamental components in life, which can significantly affect nearly all major biological processes. Future studies on NAD+ and NADH may not only elucidate some fundamental mysteries in biology, but also provide novel insights for interfering aging and many disease processes [1].

Absorption, Distribution and Excretion
It is unclear how much of the administered dose will be absorbed.

[1]. Ying W. NAD+ and NADH in cellular functions and cell death. Front Biosci. 2006 Sep 1;11:3129-48.

NADH is a coenzyme present in all living cells; it consists of two nucleotides linked by their 5'-phosphate groups, one containing an adenine base and the other containing nicotinamide. It is an important metabolite and cofactor. It is both NAD(P)H and NAD. It is the conjugate acid of NADH(2-). NADH is the reduced form of NAD+, and NAD+ is the oxidized form of NADH. NADH is a coenzyme formed by the coupling of ribosylnicotinamide 5'-bisphosphate to adenosine 5'-phosphate via a pyrophosphate bond. It is widely distributed in nature and participates in a variety of enzymatic reactions in which it acts as an electron carrier by alternating oxidation (NAD+) and reduction (NADH). NADH adds a phosphate group to the 2' position of an adenosine nucleotide via an ester bond, forming NADP. (Dorland, 27th edition) NADH is a metabolite present in or produced by Escherichia coli (K12 strain, MG1655 strain).
1,4-Dihydronicotinamide adenine dinucleotide has been reported in Arabidopsis thaliana, humans, and other organisms with relevant data.
It is a coenzyme composed of ribosylnicotinamide 5'-bisphosphate coupled to adenosine 5'-phosphate via a pyrophosphate bond. It is widely distributed in nature and participates in a variety of enzymatic reactions in which it acts as an electron carrier through alternating oxidation (NAD+) and reduction (NADH). (Dorland, 27th edition)
Pharmaceutical Indications

Some evidence suggests that NADH may help treat Parkinson's disease, chronic fatigue syndrome, Alzheimer's disease, and cardiovascular disease.
Mechanism of Action

NADH is synthesized by the human body and is therefore not an essential nutrient. Its synthesis requires the essential nutrient nicotinamide, which plays a crucial role in energy production. In addition to participating in the mitochondrial electron transport chain, NADH is also produced in the cytoplasm. The mitochondrial membrane is impermeable to NADH, and this permeability barrier effectively separates the cytoplasmic NADH pool from the mitochondrial NADH pool. However, cytoplasmic NADH can be used for bioenergy production. This occurs when the malate-aspartate shuttle introduces a reduced equivalent of NADH from the cytosol into the electron transport chain of the mitochondria. This shuttle primarily occurs in the liver and heart. Pharmacodynamics: NADH is a coenzyme composed of ribosylnicotinamide 5'-bisphosphate coupled to adenosine 5'-phosphate via a pyrophosphate bond. It is widely distributed in nature and participates in a variety of enzymatic reactions in which it acts as an electron carrier through alternating oxidation (NAD+) and reduction (NADH). The mechanism of action of NADH supplementation is not fully understood. Oral NADH supplements have been used to combat simple fatigue and some mysterious and energy-consuming diseases such as chronic fatigue syndrome and fibromyalgia. Researchers are also investigating the value of NADH supplementation in improving cognitive function in Alzheimer's patients and reducing physical disability and alleviating depressive symptoms in Parkinson's patients. Some healthy individuals also take oral NADH supplements to improve attention, memory, and exercise endurance. However, to date, no published research has demonstrated any effectiveness or safety of using NADH for these purposes.

C21H29N7O14P2

665.44

665.124

C, 37.90; H, 4.39; N, 14.73; O, 33.66; P, 9.31

58-68-4

53-84-9 (free acid); 58-68-4 (reduced); 20111-18-6 (sodium)

439153

Typically exists as solid at room temperature

2.2±0.1 g/cm3

1081.8±75.0 °C at 760 mmHg

140.0-142.0 °C
140.0 - 142.0 °C

608.0±37.1 °C

0.0±0.3 mmHg at 25°C

1.845

-4.35

8

19

11

44

1230

8

C1C=CN(C=C1C(=O)N)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)OP(=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)N4C=NC5=C(N=CN=C54)N)O)O)O)O

BOPGDPNILDQYTO-NNYOXOHSSA-N

InChI=1S/C21H29N7O14P2/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(32)14(30)11(41-21)6-39-44(36,37)42-43(34,35)38-5-10-13(29)15(31)20(40-10)27-3-1-2-9(4-27)18(23)33/h1,3-4,7-8,10-11,13-16,20-21,29-32H,2,5-6H2,(H2,23,33)(H,34,35)(H,36,37)(H2,22,24,25)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1

[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoyl-4H-pyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate

Adenosine 5'-(trihydrogen diphosphate), P'.fwdarw.5'-ester with 1,4-dihydro-1-.beta.-D-ribofuranosyl-3-pyridinecarboxamide; Adenosine 5'-(trihydrogen diphosphate), P'.fwdarw.5'-ester with 1,4-dihydro-1-beta-D-ribofuranosyl-3-pyridinecarboxamide; NADH; DPNH; 58-68-4; beta-DPNH; beta-NADH; 1,4-Dihydronicotinamide adenine dinucleotide;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)