Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:27:16 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2841
Identification
Common NameNicotinic acid
ClassSmall Molecule
DescriptionNicotinic acid, also known as niacin or vitamin B3, is a water-soluble vitamin whose derivatives such as NADH, NAD, NAD+, and NADP play essential roles in energy metabolism in the living cell and DNA repair. The designation vitamin B3 also includes the amide form, nicotinamide or niacinamide. Severe lack of niacin causes the deficiency disease pellagra, whereas a mild deficiency slows down the metabolism decreasing cold tolerance. The recommended daily allowance of niacin is 2-12 mg a day for children, 14 mg a day for women, 16 mg a day for men, and 18 mg a day for pregnant or breast-feeding women. It is found in various animal and plant tissues and has pellagra-curative, vasodilating, and antilipemic properties. The liver can synthesize niacin from the essential amino acid tryptophan (see below), but the synthesis is extremely slow and requires vitamin B6; 60 mg of tryptophan are required to make one milligram of niacin. Bacteria in the gut may also perform the conversion but are inefficient.
Compound Type
  • Antilipemic Agent
  • Cosmetic Toxin
  • Drug
  • Ester
  • Food Toxin
  • Household Toxin
  • Hypolipidemic Agent
  • Metabolite
  • Natural Compound
  • Nutraceutical
  • Organic Compound
  • Vasodilator Agent
  • Vitamin B Complex
Chemical Structure
Thumb
Synonyms
Synonym
3-Carboxylpyridine
3-Carboxypyridine
3-Pyridinecarboxylate
3-Pyridinecarboxylic acid
3-Pyridylcarboxylate
3-Pyridylcarboxylic acid
Acide Nicotinique
Acido nicotinico
Acidum Nicotinicum
Akotin
Anti-pellagra vitamin
Apelagrin
beta-Pyridinecarboxylic acid
Daskil
Efacin
Enduracin
Linic
m-Pyridinecarboxylic acid
Niac
Niacin
Niacine
Niacor
Niaspan
Nicacid
Nicamin
Nicangin
Nico-Span
Nicobid
Nicocap
Nicodelmine
Nicolar
Niconacid
Nicosan 3
Nicotinate
Nicotinipca
Nicyl
Nikotinsaeure
Nyclin
P.P. factor
Pellagra preventive factor
Pellagrin
Pelonin
PP Factor
Pyridine-beta-carboxylic acid
pyridine-β-carboxylic acid
Slo-niacin
Vitamin B3
Wampocap
β-pyridinecarboxylic acid
Chemical FormulaC6H5NO2
Average Molecular Mass123.109 g/mol
Monoisotopic Mass123.032 g/mol
CAS Registry Number59-67-6
IUPAC Namepyridine-3-carboxylic acid
Traditional Nameniacin
SMILESOC(=O)C1=CN=CC=C1
InChI IdentifierInChI=1S/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9)
InChI KeyInChIKey=PVNIIMVLHYAWGP-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyridinecarboxylic acids. Pyridinecarboxylic acids are compounds containing a pyridine ring bearing a carboxylic acid group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassPyridinecarboxylic acids and derivatives
Direct ParentPyridinecarboxylic acids
Alternative Parents
Substituents
  • Pyridine carboxylic acid
  • Heteroaromatic compound
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Fibroblasts
  • Intestine
  • Kidney
  • Liver
  • Most Tissues
  • Skeletal Muscle
  • Skin
  • Stratum Corneum
Pathways
NameSMPDB LinkKEGG Link
Nicotinate and Nicotinamide MetabolismSMP00048 map00760
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point236.6°C
Boiling PointNot Available
Solubility1.8E+004 mg/L (at 25°C)
LogP0.36
Predicted Properties
PropertyValueSource
Water Solubility83.1 g/LALOGPS
logP0.29ALOGPS
logP-0.17ChemAxon
logS-0.17ALOGPS
pKa (Strongest Acidic)2.79ChemAxon
pKa (Strongest Basic)4.19ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area50.19 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity31.16 m³·mol⁻¹ChemAxon
Polarizability11.3 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-053i-0900000000-5daf0093df6c21c7279fView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-053i-0900000000-f38b6609b45de8c74565View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0540-0900000000-4f55c81a6cd42f1b961dView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-057r-5900000000-00bf3662b5b9db533c0aView in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-0569-2900000000-7820ea736b03b71d2cb8View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0kmi-7900000000-9e4efda763cce5ddfe57View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-053i-0900000000-5daf0093df6c21c7279fView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-053i-0900000000-f38b6609b45de8c74565View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0540-0900000000-4f55c81a6cd42f1b961dView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-057r-5900000000-00bf3662b5b9db533c0aView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0569-2900000000-7820ea736b03b71d2cb8View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0540-0900000000-a701904fe6ded0abd98fView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05i0-9700000000-d7620f1dc8f42d1498b9View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-05fr-9600000000-c3303cf4e83870b3e656View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00di-1900000000-27508608b33f1fb9f221View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-003r-9100000000-a2037c9695659dceabd1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0ufr-9100000000-4a2649a83ad2a40e5194View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positivesplash10-0kmi-7900000000-1bc47d1b1850f54fb7c2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-00di-1900000000-a352c5ce16d4b682b052View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-004i-9000000000-ab23ecb032e387b40bd9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-004i-9000000000-02e37a1cfd3947037579View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-004i-9000000000-75d7e6658d2d6eca736eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0udi-9000000000-21a2d68d4f364c596f1dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-0ab9-0900000000-a74db528f61c435876c8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-00di-6900000000-773c08ab92ace4d48a9cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-00aj-9100000000-07b12fbe942e6c7fb12dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-005a-9000000000-66e0a5ba2ca8dbba1ed5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-004i-9000000000-fbf8ba47b56d7cc7be81View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-00di-0900000000-eaf82f6ab0befde118e9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Positivesplash10-00di-0900000000-eaf82f6ab0befde118e9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-004i-9300000000-b1a48f694fba565108a1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-1900000000-a352c5ce16d4b682b052View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-004i-9000000000-ab23ecb032e387b40bd9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0900000000-25068c42378f72756922View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-3900000000-6278a1e122005f48fcafView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ue9-9000000000-e4e41ed9bef32955889eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-4900000000-85d44ecd8ad348eeacd1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-9300000000-4911305982583ae20895View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-4dea4a2d4a55907605eaView in MoNA
MSMass Spectrum (Electron Ionization)splash10-0kor-8900000000-7d3f033a49f5fad75f33View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,1H] 2D NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureOral (34) ; Intramuscular (34). Both nicotinic acid and nicotinamide are efficiently absorbed from the stomach and small intestine.
Mechanism of ToxicityNiacin binds to Nicotinate D-ribonucleotide phyrophsopate phosphoribosyltransferase, Nicotinic acid phosphoribosyltransferase, Nicotinate N-methyltransferase and the Niacin receptor. Niacin is the precursor to nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are vital cofactors for dozens of enzymes. The mechanism by which niacin exerts its lipid lowering effects is not entirely understood, but may involve several actions, including a decrease in esterification of hepatic triglycerides. Niacin treatment also decreases the serum levels of apolipoprotein B-100 (apo B), the major protein component of the VLDL (very low-density lipoprotein) and LDL fractions.
MetabolismNiacin is rapidly metabolized and undergoes extensive first-pass metabolism in the liver. The drug is converted to several metabolites, including nicotinuric acid (NUA), nicotinamide, and nicotinamide adenine dinucleotide (NAD). At doses used to treat hyperlipoproteinemia, the principal metabolic pathways appear to be saturable, and niacin is thought to exhibit nonlinear, dose-dependent pharmacokinetics. (36) Half Life: 20-45 minutes.
Toxicity ValuesLD50: 7000 mg/kg (Oral, Rat) (31) LD50: 730 mg/kg (Intraperitoneal, Rat) (31) LD50: 3500 mg/kg (Subcutaneous, Mouse) (31)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of type IV and V hyperlipidemia. It is indicated as ajunctive therapy. It can be found in various foods, such as liver, chicken, beef, fish, cereal, peanuts and legumes. Niacin is also used as a pharmaceutical to reverse atherosclerosis. (14)
Minimum Risk LevelNot Available
Health EffectsNiacin at extremely high doses can have life-threatening acute toxic reactions. Extremely high doses of niacin can also cause niacin maculopathy, a thickening of the macula and retina which leads to blurred vision and blindness. This maculopathy is reversible after stopping niacin intake. Side effects of hyperglycemia, cardiac arrhythmias and birth defects have also been reported. (14)
SymptomsNicotinic acid can cause vasodilation of cutaneous blood vessels resulting in increased blood flow, principally in the face, neck and chest. This produces the niacin- or nicotinic acid-flush. The niacin-flush is thought to be mediated via the prostaglandin prostacyclin. Histamine may also play a role in the niacin-flush. Flushing is the adverse reaction first observed after intake of a large dose of nicotinic acid, and the most bothersome one.
TreatmentSupportive measures should be undertaken in the event of an overdose. (35)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00627
HMDB IDHMDB01488
PubChem Compound ID938
ChEMBL IDCHEMBL573
ChemSpider ID913
KEGG IDC00253
UniProt IDNot Available
OMIM ID100600 , 236800
ChEBI ID15940
BioCyc IDNIACINE
CTD IDNot Available
Stitch IDNiacin
PDB IDNIO
ACToR ID953
Wikipedia LinkNiacin
References
Synthesis Reference

Joseph E. Toomey, Jr., “Electrochemical synthesis of niacin and other N-heterocyclic compounds.” U.S. Patent US5002641, issued 1914.

MSDSLink
General References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S: PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med. 2003 Mar;9(3):352-5. Epub 2003 Feb 3. [12563315 ]
  4. Taggart AK, Kero J, Gan X, Cai TQ, Cheng K, Ippolito M, Ren N, Kaplan R, Wu K, Wu TJ, Jin L, Liaw C, Chen R, Richman J, Connolly D, Offermanns S, Wright SD, Waters MG: (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005 Jul 22;280(29):26649-52. Epub 2005 Jun 1. [15929991 ]
  5. Zhang Y, Schmidt RJ, Foxworthy P, Emkey R, Oler JK, Large TH, Wang H, Su EW, Mosior MK, Eacho PI, Cao G: Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A. Biochem Biophys Res Commun. 2005 Aug 26;334(2):729-32. [16018973 ]
  6. Tunaru S, Lattig J, Kero J, Krause G, Offermanns S: Characterization of determinants of ligand binding to the nicotinic acid receptor GPR109A (HM74A/PUMA-G). Mol Pharmacol. 2005 Nov;68(5):1271-80. Epub 2005 Aug 11. [16099840 ]
  7. Benyo Z, Gille A, Kero J, Csiky M, Suchankova MC, Nusing RM, Moers A, Pfeffer K, Offermanns S: GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest. 2005 Dec;115(12):3634-40. [16322797 ]
  8. Fukuwatari T, Morikawa Y, Hayakawa F, Sugimoto E, Shibata K: Influence of adenine-induced renal failure on tryptophan-niacin metabolism in rats. Biosci Biotechnol Biochem. 2001 Oct;65(10):2154-61. [11758903 ]
  9. Shin DH, Oganesyan N, Jancarik J, Yokota H, Kim R, Kim SH: Crystal structure of a nicotinate phosphoribosyltransferase from Thermoplasma acidophilum. J Biol Chem. 2005 May 6;280(18):18326-35. Epub 2005 Mar 6. [15753098 ]
  10. Zheng XQ, Hayashibe E, Ashihara H: Changes in trigonelline (N-methylnicotinic acid) content and nicotinic acid metabolism during germination of mungbean (Phaseolus aureus) seeds. J Exp Bot. 2005 Jun;56(416):1615-23. Epub 2005 Apr 18. [15837705 ]
  11. Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB: Molecular identification of high and low affinity receptors for nicotinic acid. J Biol Chem. 2003 Mar 14;278(11):9869-74. Epub 2003 Jan 9. [12522134 ]
  12. Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K: Molecular identification of nicotinic acid receptor. Biochem Biophys Res Commun. 2003 Mar 28;303(1):364-9. [12646212 ]
  13. Zellner C, Pullinger CR, Aouizerat BE, Frost PH, Kwok PY, Malloy MJ, Kane JP: Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors. Hum Mutat. 2005 Jan;25(1):18-21. [15580557 ]
  14. Nathanson JA: Caffeine and related methylxanthines: possible naturally occurring pesticides. Science. 1984 Oct 12;226(4671):184-7. [6207592 ]
  15. Gopal E, Fei YJ, Miyauchi S, Zhuang L, Prasad PD, Ganapathy V: Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family. Biochem J. 2005 May 15;388(Pt 1):309-16. [15651982 ]
  16. Salvi A, Carrupt PA, Mayer JM, Testa B: Esterase-like activity of human serum albumin toward prodrug esters of nicotinic acid. Drug Metab Dispos. 1997 Apr;25(4):395-8. [9107536 ]
  17. Hertle H, Kiese M, Renner G: Absorption in rats, dogs, pigs, and humans of nicotinic acid after oral administration of phosphatidyl inositol pentanicotinate hydrochloride (PIN). Arzneimittelforschung. 1979;29(1):114-6. [582105 ]
  18. Zarzycki PK, Kowalski P, Nowakowska J, Lamparczyk H: High-performance liquid chromatographic and capillary electrophoretic determination of free nicotinic acid in human plasma and separation of its metabolites by capillary electrophoresis. J Chromatogr A. 1995 Aug 11;709(1):203-8. [7581845 ]
  19. Hengen N, Seiberth V, Hengen M: High-performance liquid-chromatographic determination of free nicotinic acid and its metabolite, nicotinuric acid, in plasma and urine. Clin Chem. 1978 Oct;24(10):1740-3. [699281 ]
  20. Santos RD: [Pharmacology of niacin or nicotinic acid]. Arq Bras Cardiol. 2005 Oct;85 Suppl 5:17-9. Epub 2006 Jan 2. [16400392 ]
  21. Mrochek JE, Jolley RL, Young DS, Turner WJ: Metabolic response of humans to ingestion of nicotinic acid and nicotinamide. Clin Chem. 1976 Nov;22(11):1821-7. [135660 ]
  22. Pike NB: Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid. J Clin Invest. 2005 Dec;115(12):3400-3. [16322787 ]
  23. Kobayashi M, Shimizu S: [Nicotinic acid and nicotinamide]. Nihon Rinsho. 1999 Oct;57(10):2211-7. [10540864 ]
  24. Sutherland WH, Larking PW, Nye ER: Modification of nicotinic acid and prostaglandin E1 antilipolytic action in vitro. Atherosclerosis. 1976 Oct;25(1):45-53. [186078 ]
  25. Stratford MR, Dennis MF, Hoskin P, Phillips H, Hodgkiss RJ, Rojas A: Nicotinamide pharmacokinetics in humans: effect of gastric acid inhibition, comparison of rectal vs oral administration and the use of saliva for drug monitoring. Br J Cancer. 1996 Jul;74(1):16-21. [8679452 ]
  26. Angelin B, Einarsson K, Leijd B: Biliary lipid composition during treatment with different hypolipidaemic drugs. Eur J Clin Invest. 1979 Jun;9(3):185-90. [113218 ]
  27. Patterson MC, Di Bisceglie AM, Higgins JJ, Abel RB, Schiffmann R, Parker CC, Argoff CE, Grewal RP, Yu K, Pentchev PG, et al.: The effect of cholesterol-lowering agents on hepatic and plasma cholesterol in Niemann-Pick disease type C. Neurology. 1993 Jan;43(1):61-4. [8423912 ]
  28. Muller B, Kasper M, Surber C, Imanidis G: Permeation, metabolism and site of action concentration of nicotinic acid derivatives in human skin. Correlation with topical pharmacological effect. Eur J Pharm Sci. 2003 Oct;20(2):181-95. [14550884 ]
  29. Chekalina SI, Guseva LI, Bardyechev MS: [Use of nicotinic acid and midocalm for correcting blood coagulation in patients with radiation edema of the extremities]. Med Radiol (Mosk). 1985 Aug;30(8):28-30. [4033386 ]
  30. Dastur DK, Santhadevi N, Quadros EV, Avari FC, Wadia NH, Desai MN, Bharucha EP: The B-vitamins in malnutrition with alcoholism. A model of intervitamin relationships. Br J Nutr. 1976 Sep;36(2):143-59. [182198 ]
  31. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  32. McEvoy GK (ed) (2007). American Hospital Formulary Service - Drug Information 2007. Bethesda, MD: American Society of Health-System Pharmacists.
  33. Wikipedia. Niacin. Last Updated 16 December 2009.
  34. Drugs.com [Link]
  35. RxList: The Internet Drug Index (2009). [Link]
  36. Drugs.com [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Nicotinic acid receptor activity
Specific Function:
Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis. The rank order of potency for the displacement of nicotinic acid binding is 5-methyl pyrazole-3-carboxylic acid = pyridine-3-acetic acid > acifran > 5-methyl nicotinic acid = acipimox >> nicotinuric acid = nicotinamide.
Gene Name:
HCAR2
Uniprot ID:
Q8TDS4
Molecular Weight:
41849.08 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.05 uMNot AvailableBindingDB 23515
Inhibitory0.082 uMNot AvailableBindingDB 23515
Inhibitory0.104 uMNot AvailableBindingDB 23515
IC500.13 uMNot AvailableBindingDB 23515
IC500.14 uMNot AvailableBindingDB 23515
IC500.15 uMNot AvailableBindingDB 23515
IC5067.3 uMNot AvailableBindingDB 23515
References
  1. Zhang Y, Schmidt RJ, Foxworthy P, Emkey R, Oler JK, Large TH, Wang H, Su EW, Mosior MK, Eacho PI, Cao G: Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A. Biochem Biophys Res Commun. 2005 Aug 26;334(2):729-32. [16018973 ]
  2. Tunaru S, Lattig J, Kero J, Krause G, Offermanns S: Characterization of determinants of ligand binding to the nicotinic acid receptor GPR109A (HM74A/PUMA-G). Mol Pharmacol. 2005 Nov;68(5):1271-80. Epub 2005 Aug 11. [16099840 ]
  3. Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB: Molecular identification of high and low affinity receptors for nicotinic acid. J Biol Chem. 2003 Mar 14;278(11):9869-74. Epub 2003 Jan 9. [12522134 ]
  4. Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K: Molecular identification of nicotinic acid receptor. Biochem Biophys Res Commun. 2003 Mar 28;303(1):364-9. [12646212 ]
  5. Zellner C, Pullinger CR, Aouizerat BE, Frost PH, Kwok PY, Malloy MJ, Kane JP: Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors. Hum Mutat. 2005 Jan;25(1):18-21. [15580557 ]
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  19. Mahboubi K, Witman-Jones T, Adamus JE, Letsinger JT, Whitehouse D, Moorman AR, Sawicki D, Bergenhem N, Ross SA: Triglyceride modulation by acifran analogs: activity towards the niacin high and low affinity G protein-coupled receptors HM74A and HM74. Biochem Biophys Res Commun. 2006 Feb 10;340(2):482-90. Epub 2005 Dec 19. [16389067 ]
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  22. van Veldhoven JP, Blad CC, Artsen CM, Klopman C, Wolfram DR, Abdelkadir MJ, Lane JR, Brussee J, Ijzerman AP: Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A). Bioorg Med Chem Lett. 2011 May 1;21(9):2736-9. doi: 10.1016/j.bmcl.2010.11.091. Epub 2010 Nov 25. [21167710 ]
General Function:
G-protein coupled receptor activity
Specific Function:
Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet.
Gene Name:
HCAR3
Uniprot ID:
P49019
Molecular Weight:
44477.93 Da
References
  1. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S: PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med. 2003 Mar;9(3):352-5. Epub 2003 Feb 3. [12563315 ]
  2. Taggart AK, Kero J, Gan X, Cai TQ, Cheng K, Ippolito M, Ren N, Kaplan R, Wu K, Wu TJ, Jin L, Liaw C, Chen R, Richman J, Connolly D, Offermanns S, Wright SD, Waters MG: (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005 Jul 22;280(29):26649-52. Epub 2005 Jun 1. [15929991 ]
  3. Zhang Y, Schmidt RJ, Foxworthy P, Emkey R, Oler JK, Large TH, Wang H, Su EW, Mosior MK, Eacho PI, Cao G: Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A. Biochem Biophys Res Commun. 2005 Aug 26;334(2):729-32. [16018973 ]
  4. Tunaru S, Lattig J, Kero J, Krause G, Offermanns S: Characterization of determinants of ligand binding to the nicotinic acid receptor GPR109A (HM74A/PUMA-G). Mol Pharmacol. 2005 Nov;68(5):1271-80. Epub 2005 Aug 11. [16099840 ]
  5. Benyo Z, Gille A, Kero J, Csiky M, Suchankova MC, Nusing RM, Moers A, Pfeffer K, Offermanns S: GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest. 2005 Dec;115(12):3634-40. [16322797 ]
  6. Mahboubi K, Witman-Jones T, Adamus JE, Letsinger JT, Whitehouse D, Moorman AR, Sawicki D, Bergenhem N, Ross SA: Triglyceride modulation by acifran analogs: activity towards the niacin high and low affinity G protein-coupled receptors HM74A and HM74. Biochem Biophys Res Commun. 2006 Feb 10;340(2):482-90. Epub 2005 Dec 19. [16389067 ]
General Function:
Protein homodimerization activity
Specific Function:
Involved in the catabolism of quinolinic acid (QA).
Gene Name:
QPRT
Uniprot ID:
Q15274
Molecular Weight:
30845.31 Da
References
  1. Fukuwatari T, Morikawa Y, Hayakawa F, Sugimoto E, Shibata K: Influence of adenine-induced renal failure on tryptophan-niacin metabolism in rats. Biosci Biotechnol Biochem. 2001 Oct;65(10):2154-61. [11758903 ]
  2. Shin DH, Oganesyan N, Jancarik J, Yokota H, Kim R, Kim SH: Crystal structure of a nicotinate phosphoribosyltransferase from Thermoplasma acidophilum. J Biol Chem. 2005 May 6;280(18):18326-35. Epub 2005 Mar 6. [15753098 ]
  3. Zheng XQ, Hayashibe E, Ashihara H: Changes in trigonelline (N-methylnicotinic acid) content and nicotinic acid metabolism during germination of mungbean (Phaseolus aureus) seeds. J Exp Bot. 2005 Jun;56(416):1615-23. Epub 2005 Apr 18. [15837705 ]
General Function:
Nicotinamide n-methyltransferase activity
Specific Function:
Catalyzes the N-methylation of nicotinamide and other pyridines to form pyridinium ions. This activity is important for biotransformation of many drugs and xenobiotic compounds.
Gene Name:
NNMT
Uniprot ID:
P40261
Molecular Weight:
29573.705 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]