生物活性

• 描述There are two types of enzymes that affect the acetylationstate of histones: histone acetyltransferases and the opposinghistone deacetylases (HDACs). Yeast silent information regulator 2 (Sir2) is the founding member of Class III HDACs. Nonredox enzyme, sirtuin 1 (Sirt1) is an important member of the mammalian sirtuin family of proteins that commonly have dual activities as a nicotinamide adenine dinucleotide (NAD⁺)- dependent deacetylase and as a mono-ADP ribosyltransferase. Nicotinamide (NAM), a form of vitamin B3, is an inhibitor of yeast Sir2 and human Sirt1 with IC₅₀ < 50 μM. Treatment of the fetal cells with 10 mM NIC resulted in a twofold increase in DNA content and a threefold increase in insulin content and induced differentiation and maturation of human fetal pancreatic islet cells^[3]. Nicotinamide incubation (5 mM) 2h prior to hypoxia significantly increased total nicotinamide adenine dinucleotide (NADH) content, improved neuronal recovery, enhanced ATP content, and prevented NADH hyperoxidation in hippocampal slices^[4]. It was found that nicotinamide (200 mg/kg/day) treatment in Alzheimer's disease transgenic mice-drinking water from birth until 4 months of age improved both the short- and long term memory^[5].
• 作用机制Nicotinamide inhibits deacetylation by binding to a conserved pocket adjacent to NAD⁺.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  Escherichia coli BL21 (DE3) cells	-	Function assay	-	Inhibition of catalytically active human SIRT3 (102 to 399 amino acids) expressed in Escherichia coli BL21 (DE3) cells using fluorogenic 7-amino-4-methylcoumarin (AMC)-labeled peptide by fluorescence assay, IC50=6.2 μM	25275824
  human SK-MEL-28 cells	100 μM	Function assay	24 h	Reduction in ATP level in human SK-MEL-28 cells at 100 uM maintained in Locke's solution after 24 hrs by luciferase-based assay in absence of GF and glucose	22835719

• 动物研究
  剂量	Rat: 1260 mg/kg[3] (p.o.); 50 mg/kg, 500 mg/kg[4] (i.p.)
  给药途径	p.o., i.p.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00203476	Hyperlipidemia ... more >> Hypercholesterolemia Collapse <<	Phase 4	Completed	-	United States, Alabama ... more >> Tuscaloosa Research & Education Advancement Corporation Tuscaloosa, Alabama, United States, 35404 Collapse <<
  NCT03615534	Atherogenic Dyslipidemia ... more >> Obesity Associated Disorder Collapse <<	Phase 4	Completed	-	Iraq ... more >> Al Kindy College of Medicine, University of Baghdad Baghdad, Iraq, 10045 Lewai S Abdulaziz Baghdad, Iraq, 10045 Collapse <<
  NCT02061267	Metabolic Syndrome	Not Applicable	Unknown	December 2014	Spain ... more >> Instituto de la Grasa, CSIC Seville, Spain, 41012 Collapse <<

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• 参考文献

• [1] Bitterman KJ, Anderson RM, et al. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem. 2002 Nov 22;277(47):45099-107.

  [2] Otonkoski T, Beattie GM, et al. Nicotinamide is a potent inducer of endocrine differentiation in cultured human fetal pancreatic cells. J Clin Invest. 1993 Sep;92(3):1459-66

  [3] Otonkoski T, Beattie GM, Mally MI, Ricordi C, Hayek A. Nicotinamide is a potent inducer of endocrine differentiation in cultured human fetal pancreatic cells. J Clin Invest. 1993 Sep;92(3):1459-66. doi: 10.1172/JCI116723. PMID: 8104197; PMCID: PMC288291.

  [4] Shetty PK, Galeffi F, Turner DA. Nicotinamide pre-treatment ameliorates NAD(H) hyperoxidation and improves neuronal function after severe hypoxia. Neurobiol Dis. 2014 Feb;62:469-78. doi: 10.1016/j.nbd.2013.10.025. Epub 2013 Oct 31. PMID: 24184921; PMCID: PMC4143422.

  [5] Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM. Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J Neurosci. 2008 Nov 5;28(45):11500-10. doi: 10.1523/JNEUROSCI.3203-08.2008. PMID: 18987186; PMCID: PMC2617713.

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