NIFLUMIC ACID

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H9F3N2O2
Molecular Weight	282.2185
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cc(cc(c1)Nc2c(cccn2)C(=O)O)C(F)(F)F

InChI

InChIKey=JZFPYUNJRRFVQU-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12920213 | https://www.ncbi.nlm.nih.gov/pubmed/4556915 | https://www.ncbi.nlm.nih.gov/pubmed/21898399

Niflumic acid belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) and used in the treatment of rheumatoid arthritis, and joint and muscular pain. Its mechanism of action is believed to be based on selective inhibition of cycloxygenases-2 that results in antipyretic, analgesic, and anti-inflammatory effects. In addition to these effects on prostaglandin synthesis, it has been shown to act as a positive allosteric modulator on α1β2γ2 and as a negative modulator on α6β2 and α6β2γ2 (and α1β2) GABAA receptors. In addition, was reported, that niflumic acid blocked T-type calcium channels. It is available for clinical use in several European countries.

Approval Year

Targets

Primary Target	Pharmacology	Potency
Prostaglandin G/H synthase 2 46 Target ID: P35354 Gene ID: 5743.0 Gene Symbol: PTGS2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7947975	Inhibitor 7728	0.1 µM [IC50]
GABA-A receptor; alpha-1/beta-2/gamma-2 21 Target ID: CHEMBL2095172 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12920213	Positive Allosteric Modulator 157
GABA A receptor alpha-6/beta-2/gamma-2 1 Target ID: CHEMBL2111370 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12920213	Negative Allosteric Modulator 36
Voltage-gated T-type calcium channel 17 Target ID: CHEMBL2362995 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21898399	Blocker 511

Conditions

Condition	Modality	Targets	Highest Phase	Product
Joint and muscular pain 1 Sources: http://www.ndrugs.com/?s=niflamol	Primary		Approved 8043	niflamol Approved Use Unknown
Rheumatoid arthritis 294 Sources: https://www.ncbi.nlm.nih.gov/pubmed/4556915/	Palliative		Not Provided 492	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Cyclooxygenase-2 protein and prostaglandin E(2) production are up-regulated in a rat bladder inflammation model.	2001 Apr 13	11334856
Evidence for two mechanisms of amino acid osmolyte release from hippocampal slices.	2001 Aug	11512036
The disulfonic stilbene DIDS and the marine poison maitotoxin activate the same two types of endogenous cation conductance in the cell membrane of Xenopus laevis oocytes.	2001 Aug	11512026
Niflumic acid reduces the hyperpolarization-activated current (I(h)) in rod photoreceptor cells.	2001 Aug	11463484
Key role for constitutive cyclooxygenase-2 of MDCK cells in basal signaling and response to released ATP.	2001 Aug	11443051
Activation of alpha 6 GABAA receptors on depolarized cerebellar parallel fibers elicits glutamate release through anion channels.	2001 Dec	11747899
Niflumic acid modulates uncoupled substrate-gated conductances in the human glutamate transporter EAAT4.	2001 Jul 1	11432999
Chloride channel antagonists perturb growth and morphology of Neurospora crassa.	2001 Jul 24	11470368
Role of chloride in constriction of descending vasa recta by angiotensin II.	2001 Jun	11353695
Afterhyperpolarization current in myenteric neurons of the guinea pig duodenum.	2001 May	11353011
Aluminum activates a citrate-permeable anion channel in the aluminum-sensitive zone of the maize root apex. A comparison between an aluminum- sensitive and an aluminum-resistant cultivar.	2001 May	11351102
Chloride channels regulate HIT cell volume but cannot fully account for swelling-induced insulin secretion.	2001 May	11334443
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Ca2+-dependent membrane currents in vascular smooth muscle cells of the rabbit.	2001 Oct 12	11693254
Volume-activated trimethylamine oxide efflux in red blood cells of spiny dogfish (Squalus acanthias).	2001 Sep	11506995
Fenamates: a novel class of reversible gap junction blockers.	2001 Sep	11504800
Spontaneous Ca2+ activated Cl- currents in isolated urethral smooth muscle cells.	2001 Sep	11490316
Multiple transport functions of a red blood cell anion exchanger, tAE1: its role in cell volume regulation.	2001 Sep 1	11533139
Synthesis, spectral studies and anti-inflammatory activity of glycolamide esters of niflumic acid as potential prodrugs.	2002	12489252
The non-steroidal anti-inflammatory drug niflumic acid inhibits Candida albicans growth.	2002	11913762
Enhancement of HCO(3)(-) permeability across the apical membrane of bovine corneal endothelium by multiple signaling pathways.	2002 Apr	11923259
Mechanism of n-butyrate uptake in the human proximal colonic basolateral membranes.	2002 Apr	11897627
Calcium and calcium-activated currents in vagotomized rat primary vagal afferent neurons.	2002 Apr 15	11956342
The DC electrical-field-induced Ca(2+) response and growth stimulation of multicellular tumor spheroids are mediated by ATP release and purinergic receptor stimulation.	2002 Aug 15	12140258
Characterisation of the ionic currents in freshly isolated rat ureter smooth muscle cells: evidence for species-dependent currents.	2002 Dec	12466949
TRPC4 currents have properties similar to the pacemaker current in interstitial cells of Cajal.	2002 Dec	12388058
Comparative inhibitory effects of niflumic acid and novel synthetic derivatives on the rat isolated stomach fundus.	2002 Feb	11848293
Dual effect of blocking agents on Ca2+-activated Cl(-) currents in rabbit pulmonary artery smooth muscle cells.	2002 Feb 15	11850506
Stimulation of the BK(Ca) channel in cultured smooth muscle cells of human trachea by magnolol.	2002 Jan	11809993
Comparison of the osmolyte transport properties induced by trAE1 versus IClswell in Xenopus oocytes.	2002 Jan 1	11891564
Swelling-activated taurine and creatine effluxes from rat cortical astrocytes are pharmacologically distinct.	2002 Jan 15	11891574
Inhibition of gap junction hemichannels by chloride channel blockers.	2002 Jan 15	11891568
Role of Ca2+-activated Cl- channels and MLCK in slow IJP in opossum esophageal smooth muscle.	2002 Jul	12065297
Disparity between ionic mediators of volume regulation and apoptosis in N1E 115 mouse neuroblastoma cells.	2002 Jul 12	12101047
The role of prostaglandin E2 in the immunopathogenesis of experimental pulmonary tuberculosis.	2002 Jun	12047755
Control of descending vasa recta pericyte membrane potential by angiotensin II.	2002 Jun	11997323
Thermodynamic origin of the solubility profile of drugs showing one or two maxima against the polarity of aqueous and nonaqueous mixtures: niflumic acid and caffeine.	2002 Mar	11920772
Activation thresholds of K(V), BK andCl(Ca) channels in smooth muscle cells in pial precapillary arterioles.	2002 Mar-Apr	12011584
Inhibition of mycophenolic acid glucuronidation by niflumic acid in human liver microsomes.	2002 May	12012139
A Ca(2+)-inhibited non-selective cation conductance contributes to pacemaker currents in mouse interstitial cell of Cajal.	2002 May 1	11986370
D2-like dopamine receptors promote interactions between calcium and chloride channels that diminish rod synaptic transfer in the salamander retina.	2002 May-Jun	12392173
[BK channels play an important role as a negative feedback mechanism in the regulation of spontaneous rhythmic contraction of urinary bladder smooth muscles].	2002 Nov	12491797
Anion channels influence ECC by modulating L-type Ca(2+) channel in ventricular myocytes.	2002 Nov	12381751
Fenamate-induced enhancement of heterologously expressed HERG currents in Xenopus oocytes.	2002 Oct 11	12359267
Characterization of norepinephrine-evoked inward currents in interstitial cells isolated from the rabbit urethra.	2002 Sep	12176745
Separation of two Cl(-) currents in cultured human and murine mesangial cells: biophysical and pharmacological characteristics of I(Cl.vol) and I(Cl.Ca).	2002 Sep-Oct	12297705
The Entamoeba histolytica EhPgp5 (MDR-like) protein induces swelling of the trophozoites and alters chloride-dependent currents in Xenopus laevis oocytes.	2002 Spring	12002645
Ca2+-activated Cl- current in cultured myenteric neurons from murine proximal colon.	2003 Apr	12456397
Ca2+-activated Cl- channels in corpus cavernosum smooth muscle: a novel mechanism for control of penile erection.	2003 Jan	12391071
Effects of osmotic changes on the chemoreceptor cell of rat carotid body.	2003 Jan 15	12527733

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Oral

In Vitro Use Guide

Niflumic acid (100 uM) inhibits not only IL-13-induced goblet cell hyperplasia but also airway hyperresponsiveness and eosinophilic infiltration. IL-13 instillation markedly enhanced the expression of MUC5AC mRNA in the lung, and niflumic acid treatment suppressed IL-13–induced overexpression of MUC5AC. Effects of niflumic acid on MUC5AC expression were also analyzed after single IL-13 instillation, and niflumic acid suppressed overexpression of MUC5AC 24 h after IL-13.

Name

Type

Language

NIFLUMIC ACID

Official Name

English

UP-83

Code

English

NIFLUGEL

Brand Name

English

NIFLUMIC ACID [EP]

Common Name

English

NIFLUMIC ACID [EP MONOGRAPH]

Common Name

English

NIFLUMIC ACID [INN]

Common Name

English

UP 83

Code

English

NIFLUMIC ACID [MI]

Common Name

English

NSC-758196

Code

English

NIFLUMIC ACID [MART.]

Common Name

English

2-(3-(TRIFLUOROMETHYL)ANILINO)NICOTINIC ACID

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

M02AA17