Nicotinamide

• CAS: 98-92-0
• Catalog Number: ACM98920-3
• Category: Inhibitors
• Molecular Weight: 122.12
• Molecular Formula: C6H6N2O
• Description: Nicotinamide is a form of vitamin B3 or niacin. Nicotinamide Hydrochloride inhibits SIRT2 activity (IC50: 2 μM). Nicotinamide also inhibits SIRT1. Nicotinamide increases cellular NAD+, ATP, ROS levels. Nicotinamide inhibits tumor growth and improves survival. Nicotinamide also has anti-HBV activity.
• Synonyms: Aminicotin
• IUPAC Name: Pyridine-3-carboxamide
• Canonical SMILES: C1=CC(=CN=C1)C(=O)N
• InChI: InChI=1S/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9)
• InChI Key: DFPAKSUCGFBDDF-UHFFFAOYSA-N
• Boiling Point: 150-160 °C
• Melting Point: 128-131 °C(lit.)
• Flash Point: 182 °C
• Density: 1.40 g/cm³
• Solubility: Soluble in butanol, chloroform
• Appearance: White powder
• Storage: 2-8 °C
• Complexity: 114
• EC Number: 202-713-4
• Exact Mass: 122.048012819
• Hazard Statements: Xi,T,F
• Monoisotopic Mass: 122.048012819
• pKa: 3.3(at 20 °C)
• Refractive Index: 1.4660
• Safety Description: 26-36-37/39-45-36/37-16-7
• Supplemental Hazard Statements: H315-H319-H335-H225-H301+H311+H331-H370
• Symbol: GHS07,GHS02,GHS06,GHS08
• Topological Polar Surface Area: 56 Ų

Case Study

Nicotinamide: A Molecular Review of an NAD+ Precursor Vitamin in Human Nutrition

Bogan, Katrina L., and Charles Brenner. Annu. Rev. Nutr. 28.1 (2008): 115-130.

Although baseline requirements for nicotinamide adenine dinucleotide (NAD) synthesis can be met by dietary tryptophan or less than 20 mg of niacin daily (composed of niacin and/or nicotinamide), increasing evidence suggests that NAD synthesis rates may be substantially increased. Beneficial in protection against neurodegeneration, Candida glabrata infection, and possibly enhancing reverse cholesterol transport. The unique and tissue-specific biosynthetic and/or ligand activities of tryptophan, niacin, nicotinamide, and the newly identified NAD precursor nicotinamide riboside account for vitamin-specific effects and side effects. As current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD synthesis, the prospect of nicotinamide riboside supplementation in humans is raised and areas for future research are suggested.
NR is a newly discovered salvageable precursor of NAD that is found in milk. Studies in Saccharomyces cerevisiae have shown that, like Na and Nam, NR is a NAD precursor that helps maintain intracellular NAD concentrations and improves NAD-dependent activities in cells, including Sir2-dependent gene silencing and lifespan. NR can be converted to NAD via the Nrk pathway, which is induced by axotomy in dorsal root ganglion (DRG) neurons, or via the actions of nucleoside phosphorylases and nicotinamide rescue. Studies have also shown that the same two pathways required for NR rescue in yeast cells can also be used for NaR rescue. In yeast cells, NR clearly qualifies as a vitamin, as it can rescue growth of strains deficient in de novo synthesis, improve Sir2 function (8), and utilize dedicated transporters.

Research on the Effects of Nicotinamide on Central Nervous System Health

Fricker, Rosemary A., et al. International Journal of Tryptophan Research 11 (2018): 1178646918776658.

Nicotinamide, the amide form of vitamin B (niacin), has long been implicated in neuronal development, survival, and function in the central nervous system (CNS), with implications for neuronal death and neuroprotection. Research investigates the role of nicotinamide in neuronal health within the CNS, with an emphasis on studies that have shown neuroprotective effects. Nicotinamide appears to play a role in protecting neurons from traumatic injury, ischemia, and stroke, and has been implicated in 3 key neurodegenerative diseases: Alzheimer's, Parkinson's, and Huntington's. A key factor is the bioavailability of nicotinamide, with low concentrations causing neurological deficits and dementia and high concentrations potentially causing neurotoxicity. Finally, potential mechanisms of action for nicotinamide are discussed, including general maintenance of cellular energy levels and more specific inhibition of molecules such as the nicotinamide adenine dinucleotide-dependent deacetylase Sirtuin 1 (SIRT1).
Many studies suggest that nicotinamide is essential for the growth and maintenance of the CNS, promoting neuronal differentiation and neuronal survival, respectively. For example, nicotinamide appears to enhance and accelerate the conversion of embryonic stem cells to neural progenitor cells and the differentiation of neurons from precursor cells, suggesting that it plays a key role in neural development. Considerable evidence suggests that NAD+ metabolism has a direct impact on the survival of neurons in the central nervous system. NAD+ is an important substrate for 3 major enzyme classes: the sirtuin family (SIRTs), poly (ADP-ribose) polymerases (PARPs) and related adenosine diphosphate (ADP)-ribosyltransferases (ARTs), and cyclic ADP-ribose (cADPR) synthases, CD38, and CD157. Nicotinamide is a byproduct of SIRT, PARP, and ART activity. Nicotinamide can inhibit the activity of these enzymes by binding to NAD+. In addition, neurons contain only low levels of the enzyme NAMPT, which is required for the first step in the conversion of nicotinamide to NAD+, which may reduce its availability in these cells. NAD+ levels decrease with age, which may be related to reduced NAMPT levels. Further evidence supporting this comes from studies where the aminopropylcarbazole chemicals of the P7C3 class were found to exert neuroprotective effects in PD, stroke, and ALS models via activation of NAMPT.

Nicotinamide in DNA damage studies

Surjana, Devita, Gary M. Halliday, and Diona L. Damian. Journal of nucleic acids 2010.1 (2010): 157591.

Nicotinamide is the water-soluble amide form of nicotinic acid (nicotinic acid or vitamin B3). Both niacin and nicotinamide are widely found in plant and animal foods, and niacin can also be synthesized endogenously in the liver from dietary tryptophan. Nicotinamide is also used in vitamin supplements and in a range of cosmetic, hair and skin preparations. Nicotinamide is the major precursor of nicotinamide adenine dinucleotide (NAD), an essential coenzyme in ATP production and the sole substrate for the nuclear enzyme poly ADP ribose polymerase 1 (PARP-1). Numerous in vitro and in vivo studies have clearly demonstrated that PARP-1 and NAD status influence the cellular response to genotoxicity, leading to mutations and cancer formation. Nicotinamide plays an important role in preventing carcinogenesis, DNA repair, and maintaining genomic stability.
Studies have shown that cancer patients are at risk for niacin deficiency. In a trial involving 42 patients with various primary cancers, 40% of the patients were niacin deficient as measured by abnormally low levels of the niacin metabolite N-methylnicotinamide in the urine. Chemotherapy may also induce pellagra by reducing NAD levels by promoting anorexia and malabsorption. Some chemotherapy drugs (e.g., 5-fluorouracil, 6-mercaptopurine) also interfere with the conversion of tryptophan to niacin. In addition, chemotherapy alkylating agents have been shown to cause miscoding lesions, chromosomal aberrations, and secondary cancers, particularly leukemias, which complicate chemotherapy in 10%-15% of cancer survivors. More direct evidence comes from studies in rats that showed that niacin deficiency significantly increased the risk of chemotherapy-induced secondary leukemia. Niacin and NAD levels are important determinants of the genomic response to genotoxic insults. Therefore, maintaining optimal niacinamide levels is critical for cancer patients and individuals at risk for exposure to genotoxic agents.

Study on the application of niacinamide to control skin aging and pigmentation

Boo, Yong Chool. Antioxidants 10.8 (2021): 1315.

Vitamin B3 is used to synthesize the NAD family of coenzymes, which contribute to cellular energy metabolism and defense systems. Although niacinamide (nicotinamide) is mainly used as a nutritional supplement of vitamin B3, its pharmaceutical and cosmeceutical uses have been widely explored. The biological activities and cosmeceutical properties of niacinamide are discussed. Supplementation with niacinamide restores cellular NAD pools and mitochondrial energy, alleviates oxidative stress and inflammatory responses, strengthens the extracellular matrix and skin barrier, and inhibits the skin pigmentation process. In clinical trials, topical treatment with niacinamide alone or in combination with other active ingredients reduced the progression of skin aging and hyperpigmentation. Topically applied niacinamide is well tolerated by the skin. Currently, there is no convincing evidence that niacinamide has a specific molecular target for controlling skin aging and pigmentation. It is hypothesized that this substance contributes to the maintenance of skin homeostasis by regulating the redox state of cells and the various metabolites it produces. Therefore, it is suggested that niacinamide can be used as a cosmeceutical ingredient to alleviate skin aging and hyperpigmentation, especially in the elderly or in patients with reduced NAD pools in the skin due to internal or external stressors.
Nicotinamide intake can prevent lipid peroxidation and normalize decreased antioxidants and antioxidant enzymes in experimental animal models. Studies have shown that nicotinamide scavenges singlet oxygen and inhibits lipid peroxidation in rat liver microsomes induced by photosensitization of methylene blue with visible light irradiation in the presence of oxygen. Nicotinamide has also been shown to inhibit lipid peroxidation induced by NADPH/ADP-Fein rat liver microsomes. Nicotinamide inhibits lipid peroxidation and protein oxidation (carbonylation) induced by the ascorbate-Fe system in rat brain mitochondria, while no such effect was observed with niacin.

Custom Q&A

What is the molecular formula of Nicotinamide?

The molecular formula of Nicotinamide is C6H6N2O.

What are some synonyms for Nicotinamide?

Some synonyms for Nicotinamide are niacinamide, 3-Pyridinecarboxamide, and Nicotinic acid amide.

What is the molecular weight of Nicotinamide?

The molecular weight of Nicotinamide is 122.12 g/mol.

When was Nicotinamide created and modified?

Nicotinamide was created on September 16, 2004, and modified on October 21, 2023.

What is the primary significance of Nicotinamide?

The primary significance of Nicotinamide is in the prevention and/or cure of blacktongue and pellagra.

What are some functions of Nicotinamide?

Nicotinamide functions as an EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor, a metabolite, a cofactor, an antioxidant, a neuroprotective agent, an EC 3.5.1.98 (histone deacetylase) inhibitor, an anti-inflammatory agent, a Sir2 inhibitor, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite, a mouse metabolite, a human urinary metabolite, and a geroprotector.

What is the IUPAC name of Nicotinamide?

The IUPAC name of Nicotinamide is pyridine-3-carboxamide.

What is the InChI of Nicotinamide?

The InChI of Nicotinamide is InChI=1S/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9).

What is the InChIKey of Nicotinamide?

The InChIKey of Nicotinamide is DFPAKSUCGFBDDF-UHFFFAOYSA-N.

What is the CAS number of Nicotinamide?

The CAS number of Nicotinamide is 98-92-0.

Synthetic Use

Upstream Synthesis Route 1

• 56-85-9

• 98-92-0

Reference: [1]Biochemical Journal,1949,vol. 44,p. 506 - 509

Downstream Synthesis Route 1

• 98-92-0

• 13438-65-8

Reference: [1] Journal of the American Chemical Society, 1944, vol. 66, p. 1479,1482
[2] Journal of Organic Chemistry, 1954, vol. 19, p. 1633,1636[3] Org. Synth. Coll., 1963, vol. Vol. IV, p. 166

Downstream Synthesis Route 2

• 98-92-0
• 121-69-7

• 13438-65-8

Reference: [1] Journal of the American Chemical Society, 1944, vol. 66, p. 1479,1482

Downstream Synthesis Route 3

• 98-92-0

• 100-55-0

Reference: [1] ACS Catalysis, 2016, vol. 6, # 1, p. 47 - 54
[2] Chemical Science, 2017, vol. 8, # 5, p. 3576 - 3585

Downstream Synthesis Route 4

• 590-92-1
• 98-92-0

• 109822-09-5

Reference: [1]Justus Liebigs Annalen der Chemie,1959,vol. 621,p. 106,119

Downstream Synthesis Route 5

• 50-00-0
• 98-92-0

• 3569-99-1

Reference: [1]Roczniki Chemii,1953,vol. 27,p. 396,401
Chem.Abstr.,1955,p. 1033
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2005,vol. 44,p. 158 - 162
[3]Journal of Chemical Sciences,2014,vol. 126,p. 1285 - 1290

* For details of the synthesis route, please refer to the original source to ensure accuracy.