Endogenous Metabolite
β-Nicotinamide mononucleotide is an intermediate in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). It acts as a precursor to NAD+, thereby influencing NAD+-dependent enzymes such as sirtuins (SIRT1, SIRT3), poly ADP-ribose polymerase (PARP), and CD38. [1]

β-Nicotinamide mononucleotide has numerous advantageous pharmacological properties. Participation in NAD+ production is the primary mechanism by which NMN carries out its pharmacological effect. This mechanism is involved in cell biochemical processes, cardioprotection, diabetes, Alzheimer's disease, and issues connected to obesity [1]. While NAD+ levels were dramatically decreased by providing the NAD+ precursor NAM or NMN (0.5–1 mM), intracellular NAD+ levels were significantly decreased by knocking down or knocking out Nampt (KD or KO) or by treatment with the Nampt inhibitor FK866. Boost. CD8+ T cell activation and activity are inhibited by treatment with the NAD+ precursor NMN [2].

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In a study using organotypic hippocampal slice cultures (OHCs), β-Nicotinamide mononucleotide decreased Aβ oligomer-induced cell death by 65% in an Aβ oligomer infusion Alzheimer's disease model. [1]
In yeast and human cells, nicotinamide riboside (NR) is phosphorylated by nicotinamide riboside kinases (NRK1 and NRK2) to form NMN, which is then converted to NAD+. [1]

Dox-induced cardiac dysfunction and mtDNA damage are prevented by β-nicotinamide mononucleotide (500 mg/kg; intraperitoneal injection; three times a week for 7–10 weeks) [3]. While Nampt metabolite β-nicotinamide mononucleotide (300 mg/kg body weight; i.p.; every two days for two weeks) greatly enhanced tumor growth in C57BL/6 mice (carrying wild-type type Hepa1-6 cells), Nampt KO considerably prevented tumor progression. shown variations in NAD+ levels in tumors treated with β-nicotinamide mononucleotide and Nampt KO [2]. In HFD-induced T2D animals, β-nicotinamide mononucleotide restores NAD+ levels, thereby mitigating glucose intolerance. Additionally, by partially activating SIRT1, β-nicotinamide mononucleotide improves hepatic insulin sensitivity and restores gene expression linked to oxidative stress, inflammatory response, and circadian rhythms [4].

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NAD+ availability decreases with age and in certain disease conditions. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been shown to enhance NAD+ biosynthesis and ameliorate various pathologies in mouse disease models. In this study, we conducted a 12-month-long NMN administration to regular chow-fed wild-type C57BL/6N mice during their normal aging. Orally administered NMN was quickly utilized to synthesize NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated physiological decline in mice. Without any obvious toxicity or deleterious effects, NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies. Consistent with these phenotypes, NMN prevented age-associated gene expression changes in key metabolic organs and enhanced mitochondrial oxidative metabolism and mitonuclear protein imbalance in skeletal muscle. These effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans. Cell Metab. 2016 Dec 13;24(6):795-806.

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In a murine model of transient forebrain ischemia, intraperitoneal administration of β-Nicotinamide mononucleotide (62.5 mg/kg) improved neurological outcomes and reduced hippocampal CA1 neuronal death after reperfusion. It also reduced poly-ADP-ribosylation (PAR) formation and NAD+ catabolism. [1]
In a collagenase-induced intracerebral hemorrhage (ICH) mouse model, intraperitoneal β-Nicotinamide mononucleotide (300 mg/kg) administered 30 minutes post-ICH increased intracerebral NAD+ levels at 2 and 6 hours, and reduced edema, neuronal death, ROS content, neuroinflammation, and microglia activation. [1]
In high-fat diet-induced diabetic mice, intraperitoneal β-Nicotinamide mononucleotide (500 mg/kg/day) for 7–10 days improved insulin intolerance and glucose homeostasis. [1]
In aged mice, long-term oral administration of β-Nicotinamide mononucleotide (100 or 300 mg/kg/day for 12 months) reduced age-associated weight gain, improved metabolic parameters, and reversed age-related gene expression changes in skeletal muscle, white adipose tissue, and liver. [1]

Nicotinamide mononucleotide has a role as an Escherichia coli metabolite and a mouse metabolite. It is a conjugate base of a NMN(+). It is a conjugate acid of a NMN(-).
Nicotinamide ribotide is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).

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In bacterial systems such as Francisella tularensis, nicotinic acid mononucleotide is amidated to NMN by NMN synthetase, followed by adenylation to NAD+ by NMN adenyltransferase. [1]
In mammalian cells, nicotinamide phosphoribosyltransferase catalyzes the conversion of nicotinamide to NMN, which is then adenylated to NAD+ by nicotinamide mononucleotide adenylyltransferase (NMNAT). [1]

For assessing PD-L1 induction, cancer cells (e.g., Hepa1-6, LLC, B16, Pan02) were pretreated with β-Nicotinamide mononucleotide (0.5-1 mM) for a specified period (e.g., 24h), followed by stimulation with recombinant IFNγ (100 ng/mL). After stimulation (e.g., 24h), cells were harvested for analysis. Surface PD-L1 protein expression was measured by flow cytometry using fluorochrome-conjugated anti-PD-L1 antibodies. For mRNA analysis, total RNA was extracted, reverse transcribed, and target gene (e.g., PD-L1, IRF1) transcript levels were quantified by real-time PCR using SYBR Green Master Mix. For protein level analysis (e.g., p-STAT1, STAT1, IRF1, TET1), whole cell lysates were prepared, and proteins were separated by SDS-PAGE, transferred to PVDF membranes, and detected using specific primary antibodies and fluorescent secondary antibodies visualized with an Odyssey scanner. For co-immunoprecipitation assays, cell lysates were incubated with anti-TET1 antibody overnight at 4°C, followed by pull-down with protein G magnetic beads. Precipitated proteins were analyzed by immunoblotting. [2]

Animal/Disease Models: C57BL6 mice (p53−/− mice) [3]
Doses: 500 mg/kg
Route of Administration: intraperitoneal (ip) injection; 3 times a week for 7-10 weeks
Experimental Results: Protection against Dox-treated p53−/− The cardiac function of mice Dramatically diminished (weeks 7 and 10 of the study), while the doxorubicin (Dox)-induced attenuation of mitochondrial respiration and tissue ATP depletion were rescued).

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Type 2 diabetes (T2D) has become epidemic in our modern lifexstyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD(+) biosynthesis, and the NAD(+)-dependent protein deacetylase SIRT1. Here, we show that NAMPT-mediated NAD(+) biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD(+) intermediate, ameliorates glucose intolerance by restoring NAD(+) levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD(+) and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a potential nutriceutical intervention against diet- and age-induced T2D.[4]

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In a study on myocardial ischemia-reperfusion injury, mice received intraperitoneal β-Nicotinamide mononucleotide (500 mg/kg) either 30 minutes before ischemia or every 6 hours during a 24-hour reperfusion period. [1]
In a study on Alzheimer's disease-relevant mice, β-Nicotinamide mononucleotide was administered to assess mitochondrial oxygen consumption rates and morphology. [1]
In aged C57BL/6 mice, β-Nicotinamide mononucleotide was administered orally at 300 mg/kg/day for 8 weeks to assess vascular function. [1]

In mouse models, β-nicotinamide mononucleotide (NMN) is absorbed from the intestine into the bloodstream within 2-3 minutes after oral administration and is completely absorbed by tissues within 15 minutes. It is rapidly converted into NAD+ in tissues such as the liver, skeletal muscle, and cortex. [1]
Before entering mammalian cells, NMN is dephosphorylated to nicotinamide nucleoside (NR) by the extracellular enzyme CD73. NR is then transported into the cell via the balanced nucleoside transporter (ENT) and reconverted into NMN by NRK1. [1]

β-Nicotinamide mononucleotide (NR) has been reported to have fewer adverse side effects compared to other NAD+ precursors such as nicotinic acid and nicotinamide. [1] A 12-week study of NR supplementation (2000 mg/day) in obese patients showed no improvement in glucose metabolism, but good safety, indicating that the relevant NAD+ precursor has a good safety profile. [1]

[1]. Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule. Biomolecules. 2019;9(1):34. Published 2019 Jan 21.

[2]. NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion [published online ahead of print, 2020 Nov 3]. Cell Metab. 2020;S1550-4131(20)30554-4.

[3]. p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities. Proc Natl Acad Sci U S A. 2019;116(39):19626-19634.

[4]. Yoshino J, et al Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536.

NMN zwitterion is a nicotinamide mononucleotide. It is a metabolite of both E. coli and mice. It is the conjugate base of NMN(+) and the conjugate acid of NMN(-). Nicotinamide ribonucleotide is a metabolite found or produced by E. coli (K12 strain, MG1655 strain). Nicotinamide mononucleotide has also been reported in fruit flies, humans, and other organisms with relevant data. Nicotinamide ribonucleotide is a metabolite found or produced by Saccharomyces cerevisiae. 3-Carbamoyl-1-β-D-furanose ribosylpyridine hydroxide-5'-phosphate, inner salt. β-Nicotinamide mononucleotide is a nucleotide in which the nitrogenous base nicotinamide is linked to the C-1 position of the D-ribose by a β-N-glycosidic bond. Synonyms: Nicotinamide ribonucleotide; NMN.

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β-Nicotinamide mononucleotide is a naturally occurring nucleotide found in foods such as broccoli, avocado, tomatoes, and raw beef. [1]
Its potential for treating age-related diseases, diabetes, and neurodegenerative diseases is currently being investigated in several clinical trials (e.g., NCT03151239, UMIN000021309). [1]
In preclinical models, it has shown potential for cardioprotective, neuroprotective, antidiabetic, anti-obesity, and anti-aging effects, primarily through increasing NAD+ levels and activating the sirtuin pathway. [1]

C11H15N2O8P

334.2192

334.056

C, 39.53; H, 4.52; N, 8.38; O, 38.30; P, 9.27

1094-61-7

14180

White to off-white solid powder

-3.38

4

8

5

22

455

4

C1=CC(=C[N+](=C1)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)[O-])O)O)C(=O)N

DAYLJWODMCOQEW-TURQNECASA-N

InChI=1S/C11H15N2O8P/c12-10(16)6-2-1-3-13(4-6)11-9(15)8(14)7(21-11)5-20-22(17,18)19/h1-4,7-9,11,14-15H,5H2,(H3-,12,16,17,18,19)/t7-,8-,9-,11-/m1/s1

((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl hydrogen phosphate

β-nicotinamide mononucleotide; NMN; β-Nicotinamide mononucleotide; Nicotinamide Mononucleotide; beta-Nicotinamide mononucleotide; nicotinamide mononucleotide; NMN zwitterion; beta-NMN; Nicotinamide ribotide; NMN; nicotinamide nucleotide; β-NMN; β-NM;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

H2O : ~83.33 mg/mL (~249.33 mM)

Solubility in Formulation 1: 100 mg/mL (299.20 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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