Identification

Name
Niflumic Acid
Accession Number
DB04552  (EXPT02331)
Type
Small Molecule
Groups
Experimental
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 IDs
Lopac-N-0630 / UP 83
International/Other Brands
Niflam / Niflugel / Nifluril
Categories
UNII
4U5MP5IUD8
CAS number
4394-00-7
Weight
Average: 282.218
Monoisotopic: 282.061612157
Chemical Formula
C13H9F3N2O2
InChI Key
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

Pharmacology

Indication

Used in the treatment of rheumatoid arthritis.

Pharmacodynamics

Niflumic acid, a nonsteroidal anti-inflammatory fenamate, is a Ca2+-activated Cl- channel blocker.

Mechanism of action

Niflumic acid is able to inhibit both phospholipase A2 as well as COX-2, thereby acting as an antiinflamatory and pain reduction agent.

TargetActionsOrganism
APhospholipase A2
inhibitor
Human
AProstaglandin G/H synthase 2
inhibitor
Human
UChloride channel protein ClC-Ka
inducer
Human
UProstaglandin G/H synthase 1Not AvailableHuman
UCytosolic phospholipase A2Not AvailableHuman
UUDP-glucuronosyltransferase 1-9Not AvailableHuman
Absorption

Well absorbed following oral administration.

Volume of distribution
Not Available
Protein binding

90% bound to plasma proteins.

Metabolism

Hepatic.

Route of elimination
Not Available
Half life

2.5 hours

Clearance
Not Available
Toxicity

Oral, mouse: LD50 = 350 mg/kg; Oral, rat: LD50 = 250 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when (4R)-limonene is combined with Niflumic Acid.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when Niflumic Acid is combined with 16-Bromoepiandrosterone.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when Niflumic Acid is combined with 19-norandrostenedione.
5-androstenedioneThe risk or severity of adverse effects can be increased when Niflumic Acid is combined with 5-androstenedione.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Niflumic Acid is combined with Abciximab.
AcebutololNiflumic Acid may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Niflumic Acid is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Niflumic Acid is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when Niflumic Acid is combined with Acenocoumarol.
AcetaminophenNiflumic Acid may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

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
Human Metabolome Database
HMDB0015573
KEGG Compound
C13698
PubChem Compound
4488
PubChem Substance
46504657
ChemSpider
4333
BindingDB
85507
ChEBI
34888
ChEMBL
CHEMBL63323
Therapeutic Targets Database
DAP000972
PharmGKB
PA164746749
IUPHAR
2439
Guide to Pharmacology
GtP Drug Page
HET
NFL
Wikipedia
Niflumic_acid
ATC Codes
M02AA17 — Niflumic acidM01AX02 — Niflumic acid
PDB Entries
1td7 / 2wm3
MSDS
Download (73.3 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)203 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Download (9.79 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001r-0090000000-d212523eaa8e47f9054f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000i-0090000000-7f1bc979a7f8c7077a95
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000i-0090000000-dd0310ff257f2921383c
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000i-0490000000-b0e41ea5dbccc5a0b0f6
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004r-1980000000-1096f092d7eef8500782
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-2930000000-038c8f35115d57e400ee
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004l-4900000000-c2e52373f3300219b388
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0g6u-9700000000-a47c140f0903976ebc7f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00dj-9200000000-4a59d785457835ab936e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0090000000-1d2a69ae63d48722b5c1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0190000000-30b3c58f88b7803349dd
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014j-0960000000-b837ec0e3f19a1b86316
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0090000000-065361d6324d9eb6997f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00lr-0090000000-339e0764e241daa8de0a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0090000000-72bb52f92fc53b179b00
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0190000000-7e1966497ac2f37804a2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kb-0690000000-30e96da9f66c54d2cea7
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kb-1930000000-0b215b890ef639ace9db
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00vm-2900000000-7889ec00129ecfe21759
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-8900000000-bdc72e63ea5feea2f90d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-9400000000-03798ba57e12a1f6bf35
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0159-0090000000-429b0738786cba43f8d7
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014j-2690000000-7b7c343f3f0b113fd715

Taxonomy

Description
This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Trifluoromethylbenzenes
Direct Parent
Trifluoromethylbenzenes
Alternative Parents
Pyridinecarboxylic acids / Aniline and substituted anilines / Aminopyridines and derivatives / Imidolactams / Vinylogous amides / Heteroaromatic compounds / Amino acids / Secondary amines / Azacyclic compounds / Carboxylic acids
show 7 more
Substituents
Trifluoromethylbenzene / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Aniline or substituted anilines / Aminopyridine / Pyridine / Imidolactam / Vinylogous amide / Heteroaromatic compound / Amino acid or derivatives
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyridines, aromatic carboxylic acid (CHEBI:34888)

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
Uniprot Name
Phospholipase A2
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...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
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...
Gene Name
CLCNKA
Uniprot ID
P51800
Uniprot Name
Chloride channel protein ClC-Ka
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 gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
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...
Gene Name
PLA2G4A
Uniprot ID
P47712
Uniprot Name
Cytosolic phospholipase A2
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 trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
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 leucin...
Gene Name
SLC16A7
Uniprot ID
O60669
Uniprot Name
Monocarboxylate transporter 2
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 leucin...
Gene Name
SLC16A1
Uniprot ID
P53985
Uniprot Name
Monocarboxylate transporter 1
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]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 13:52