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Nicotinamide-d4 is intended for use as an internal standard for the quantification of nicotinamide by GC- or LC-MS. Nicotinamide is an amide form of niacin, which is also known as vitamin B3, that can be biosynthesized in vivo or obtained through the diet.1 It is a precursor in the synthesis of the metabolic cofactor NAD+ and an inhibitor of sirtuin 1 (SIRT1; IC50 = <50 μM).2 Nicotinamide (10 μM) increases the activity of serine palmitoyltransferase (SPT) and the biosynthesis of ceramide, glucosylceramide, sphingomyelin, free fatty acids, and cholesterol in primary human keratinocytes.3 Nicotinamide (40 μM) induces apoptosis in SNU-398, SNU-739, and HepG2 hepatocellular carcinoma (HCC) cells, and it prevents the formation of neoplastic lesions in a diethylnitrosamine-induced mouse model of HCC.4 Unlike niacin, nicotinamide does not reduce plasma lipid levels or induce flushing.5,6,7

1.Li, F., Chong, Z.Z., and Maiese, K.Cell life versus cell longevity: The mysteries surrounding the NAD+ precursor nicotinamideCurr. Med. Chem.13(8)883-895(2006) 2.Bitterman, K.J., Anderson, R.M., Cohen, H.Y., et al.Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1J. Biol. Chem.277(47)45099-45107(2002) 3.Tanno, O., Ota, Y., Kitamura, N., et al.Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrierBr. J. Dermatol.143(3)524-531(2000) 4.Park, S.Y., Lee, K.B., Lee, M.-J., et al.Nicotinamide inhibits the early stage of carcinogen-induced hepatocarcinogenesis in mice and suppresses human hepatocellular carcinoma cell growthJ. Cell. Physiol.227(3)899-908(2012) 5.Lukasova, M., Hanson, J., Tunaru, S., et al.Nicotinic acid (niacin): New lipid-independent mechanisms of action and therapeutic potentialsTrends Pharmacol. Sci.32(12)700-707(2011) 6.Bodor, E.T., and Offermanns, S.Nicotinic acid: An old drug with a promising futureBr. J. Pharmacol.153(Suppl 1)S68-S75(2008) 7.Haining, C.G.Effects of anti-rheumatic compounds and pyridine derivatives on the cutaneous response to thurfyl nicotinate in the guinea-pigBr. J. Pharmacol. Chemother.21(1)104-112(1963)

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