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Identification
NameNiflumic Acid
Accession NumberDB04552  (EXPT02331)
TypeSmall Molecule
GroupsApproved
Description

An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis. [PubChem]

Structure
Thumb
Synonyms
Acide niflumique
Acido niflumico
Acidum niflumicum
NFA
Niflugel
External Identifiers
  • Lopac-N-0630
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
NiflamNot Available
NiflugelNot Available
NiflurilNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNII4U5MP5IUD8
CAS number4394-00-7
WeightAverage: 282.218
Monoisotopic: 282.061612157
Chemical FormulaC13H9F3N2O2
InChI KeyInChIKey=JZFPYUNJRRFVQU-UHFFFAOYSA-N
InChI
InChI=1S/C13H9F3N2O2/c14-13(15,16)8-3-1-4-9(7-8)18-11-10(12(19)20)5-2-6-17-11/h1-7H,(H,17,18)(H,19,20)
IUPAC Name
2-{[3-(trifluoromethyl)phenyl]amino}pyridine-3-carboxylic acid
SMILES
OC(=O)C1=C(NC2=CC=CC(=C2)C(F)(F)F)N=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyridinecarboxylic acids. These 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
  • Aminopyridine
  • Imidolactam
  • Benzenoid
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Vinylogous amide
  • Azacycle
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed in the treatment of rheumatoid arthritis.
PharmacodynamicsNiflumic acid, a nonsteroidal anti-inflammatory fenamate, is a Ca2+-activated Cl- channel blocker.
Mechanism of actionNiflumic acid is able to inhibit both phospholipase A2 as well as COX-2, thereby acting as an antiinflamatory and pain reduction agent.
Related Articles
AbsorptionWell absorbed following oral administration.
Volume of distributionNot Available
Protein binding90% bound to plasma proteins.
Metabolism

Hepatic.

Route of eliminationNot Available
Half life2.5 hours
ClearanceNot Available
ToxicityOral, mouse: LD50 = 350 mg/kg; Oral, rat: LD50 = 250 mg/kg
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9298
Blood Brain Barrier+0.9115
Caco-2 permeable+0.5318
P-glycoprotein substrateNon-substrate0.7803
P-glycoprotein inhibitor INon-inhibitor0.8783
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.9236
CYP450 2C9 substrateNon-substrate0.7654
CYP450 2D6 substrateNon-substrate0.8881
CYP450 3A4 substrateNon-substrate0.776
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.7762
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7812
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8322
BiodegradationNot ready biodegradable0.992
Rat acute toxicity3.0838 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.988
hERG inhibition (predictor II)Non-inhibitor0.7993
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point203 °CNot Available
water solubility19 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.43TAKACS-NOVAK,K ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0883 mg/mLALOGPS
logP4.33ALOGPS
logP3.12ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)1.88ChemAxon
pKa (Strongest Basic)5.51ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area62.22 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity65.93 m3·mol-1ChemAxon
Polarizability24.21 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.79 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  1. Criddle DN, de Moura RS, Greenwood IA, Large WA: Inhibitory action of niflumic acid on noradrenaline- and 5-hydroxytryptamine-induced pressor responses in the isolated mesenteric vascular bed of the rat. Br J Pharmacol. 1997 Mar;120(5):813-8. [PubMed:9138686 ]
External Links
ATC CodesM02AA17M01AX02
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (73.3 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Receptor binding
Specific Function:
PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides, this releases glycerophospholipids and arachidonic acid that serve as the precursors of signal molecules.
Gene Name:
PLA2G1B
Uniprot ID:
P04054
Molecular Weight:
16359.535 Da
References
  1. Jabeen T, Singh N, Singh RK, Sharma S, Somvanshi RK, Dey S, Singh TP: Non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase A2: structure of the complex of phospholipase A2 with niflumic acid at 2.5 Angstroms resolution. Acta Crystallogr D Biol Crystallogr. 2005 Dec;61(Pt 12):1579-86. Epub 2005 Nov 19. [PubMed:16301791 ]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
References
  1. Jabeen T, Singh N, Singh RK, Sharma S, Somvanshi RK, Dey S, Singh TP: Non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase A2: structure of the complex of phospholipase A2 with niflumic acid at 2.5 Angstroms resolution. Acta Crystallogr D Biol Crystallogr. 2005 Dec;61(Pt 12):1579-86. Epub 2005 Nov 19. [PubMed:16301791 ]
  2. Diao HL, Zhu H, Ma H, Tan HN, Cong J, Su RW, Yang ZM: Rat ovulation, implantation and decidualization are severely compromised by COX-2 inhibitors. Front Biosci. 2007 May 1;12:3333-42. [PubMed:17485303 ]
  3. Alpert E, Gruzman A, Tennenbaum T, Sasson S: Selective cyclooxygenase-2 inhibitors stimulate glucose transport in L6 myotubes in a protein kinase Cdelta-dependent manner. Biochem Pharmacol. 2007 Feb 1;73(3):368-77. Epub 2006 Oct 13. [PubMed:17098211 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Voltage-gated chloride channel activity
Specific Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.
Gene Name:
CLCNKA
Uniprot ID:
P51800
Molecular Weight:
75284.08 Da
References
  1. Picollo A, Liantonio A, Babini E, Camerino DC, Pusch M: Mechanism of interaction of niflumic acid with heterologously expressed kidney CLC-K chloride channels. J Membr Biol. 2007 Apr;216(2-3):73-82. Epub 2007 Jul 21. [PubMed:17659402 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
References
  1. Talbot S, Lin JC, Lahjouji K, Roy JP, Senecal J, Morin A, Couture R: Cigarette smoke-induced kinin B1 receptor promotes NADPH oxidase activity in cultured human alveolar epithelial cells. Peptides. 2011 Jul;32(7):1447-56. doi: 10.1016/j.peptides.2011.05.005. Epub 2011 May 11. [PubMed:21600945 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Phospholipase a2 activity
Specific Function:
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response.
Gene Name:
PLA2G4A
Uniprot ID:
P47712
Molecular Weight:
85238.2 Da
References
  1. Jabeen T, Singh N, Singh RK, Sharma S, Somvanshi RK, Dey S, Singh TP: Non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase A2: structure of the complex of phospholipase A2 with niflumic acid at 2.5 Angstroms resolution. Acta Crystallogr D Biol Crystallogr. 2005 Dec;61(Pt 12):1579-86. Epub 2005 Nov 19. [PubMed:16301791 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Retinoic acid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular Weight:
59940.495 Da
References
  1. Mano Y, Usui T, Kamimura H: In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant human UDP-glucuronosyltransferase 1A9--potent inhibition by niflumic acid. Biopharm Drug Dispos. 2006 Jan;27(1):1-6. [PubMed:16278927 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Symporter activity
Specific Function:
Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Functions as high-affinity pyruvate transporter.
Gene Name:
SLC16A7
Uniprot ID:
O60669
Molecular Weight:
52199.745 Da
References
  1. Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW: Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. [PubMed:10417314 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Symporter activity
Specific Function:
Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bod...
Gene Name:
SLC16A1
Uniprot ID:
P53985
Molecular Weight:
53943.685 Da
References
  1. Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW: Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. [PubMed:10417314 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:24