Disease relevance of niflumic acid

• METHODS: The effects of niflumic acid (NA), a relatively specific blocker of calcium-activated chloride channel (CLCA), on goblet cell hyperplasia, eosinophil accumulation, and airway hyperresponsiveness were evaluated after IL-13 instillation into the airways [1].
• In contrast, 9AC and niflumic acid reduced the amplitude of the STDs and blocked the action potentials [2].
• Short-term niflumic-acid-induced acute renal failure in children [3].
• The same observation, i.e., reduction of excitotoxic edema formation but no effect on ischemia-induced edema, was made with chloride transport inhibitors such as DIDS and niflumic acid [4].
• Neither sodium salicylate nor the cyclooxygenase-2 inhibitor, niflumic acid, protected motor neurons from the toxicity of mutated Cu/Zn-superoxide dismutase (SOD-1) linked to a familial form of the motor neuron disease, amyotrophic lateral sclerosis [5].

High impact information on niflumic acid

• Speract-induced fluctuations were sensitive to membrane potential and calcium channel blockers, and were potentiated by niflumic acid, an anion channel blocker [6].
• The capability to inhibit GCAC1 increases in a dose-dependent manner in the sequence: probenecid less than A-9-C less than ethacrynic acid less than niflumic acid less than IAA-94 less than NPPB [7].
• IT was also blocked by the chloride channel blockers DIDS (10(-4) mol/L) and niflumic acid (10(-5) mol/L) [8].
• Niflumic acid-treated PMNs also had impaired transendothelial migration in vitro, whereas migration in vivo was not altered in Clcn3((-/-)) PMNs [9].
• Furthermore, these currents were inhibited by the chloride channel blocker niflumic acid [10].

Chemical compound and disease context of niflumic acid

• In our study, the effects of TNF-alpha, inhibitors of arachidonic acid (AA) metabolism (baicalein, BA; indomethacin, INDO; niflumic acid, NA; nordihydroguaiaretic acid, NDGA), and/or their combinations on undifferentiated or sodium butyrate (NaBt)-differentiated human colon adenocarcinoma HT-29 cells were compared [11].
• METHODS: Breast cancer cells (Hs578T, MDA-MB-231 and MCF-7) were treated with selective COX-2 inhibitors (NS-398 and Niflumic acid, NA) [12].
• Data from experiments performed on neutrophils treated with pertussis toxin, staurosporine, propranolol or niflumic acid suggest that modulation of phospholipase D and A2 activities could be involved in the modification by LDL of leukocyte response to formyl-Met-Leu-Phe [13].

Biological context of niflumic acid

• The other Cl- channel blockers produced a very different pattern for the inhibitory dose dependence of secretion, with IC50 values for NPPB, niflumic acid, and NPAA of 23, 60, and 180 microM, respectively [14].
• Niflumic acid suppresses interleukin-13-induced asthma phenotypes [1].
• The Ca2+-activated Cl- channel (CLCA) inhibitor, niflumic acid (NFA, 100 microM), significantly reduced BK-induced action potential discharge to 21 +/- 7% of the control BK response [15].
• Our experiments demonstrate that VSOAC currents in myocytes from Clcn3(+/+) and Clcn3(-/-) mice are remarkably similar in terms of activation and inactivation kinetics, steady-state current densities, rectification, anion selectivity (I(-) > Cl(-)>> Asp(-)) and sensitivity to block by glibenclamide, niflumic acid, DIDS and extracellular ATP [16].
• This vasoconstriction was markedly attenuated by lowering the extracellular calcium concentration, by the L-type calcium channel blocker amlodipine or by the chloride channel blocker niflumic acid [17].

Anatomical context of niflumic acid

• We examined the voltage-dependent block of Ca(2+)-activated Cl(-) channels by anthacene-9-carboxylic acid (A9C), diphenylamine-2-carboxylic acid (DPC), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and niflumic acid (NFA) in excised inside-out and outside-out patches from Xenopus oocytes [18].
• Inhibition of transport into infected cells was also observed with phloretin, furosemide, niflumic acid, stilbenedisulfonate derivatives, and 5-nitro-2-(3-phenylpropylamino)benzoic acid at concentrations similar to those that inhibit the lactate carrier of control erythrocytes [19].
• A range of inhibitors of MCT1, including alpha-cyanocinnamate derivatives, phloretin, and niflumic acid, inhibited hepatocyte MCT with K0.5 values significantly higher than for tumor cell MCT1, while stilbene disulfonate derivatives and p-chloromercuribenzene sulfonate had similar K0.5 values in both cell types [20].
• RESULTS: The inhibitors niflumic acid, nimesulide and rofecoxib increased the rate of hexose uptake in L6 myotubes in the absence of insulin and in a dose- and time-dependent manner [21].
• Dynamics of Ca2+-dependent Cl- channel modulation by niflumic acid in rabbit coronary arterial myocytes [22].

Associations of niflumic acid with other chemical compounds

• The electrical-field-evoked Ca(2+) response as well as c-Fos activation and growth stimulation of tumor spheroids were inhibited by pretreatment with the anion channel blockers NPPB, niflumic acid and tamoxifen [23].
• The effects of niflumic acid and flufenamic acid, two nonsteroidal anti-inflammatory agents known to block anion transport in red blood cells, on Ca2(+)-activated Cl- currents (ICl(Ca)) in Xenopus oocytes were examined [24].
• CDPG-induced currents were reduced or abolished by pretreatment with thapsigargin, by injection of the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, or by extracellular perfusion of the Cl- channel blocker niflumic acid but were insensitive to injection of the InsP3 antagonist heparin [25].
• Dexamethasone and niflumic acid, a cyclooxygenase-2 inhibitor, both inhibited haptoglobin release [26].
• Two classes of compounds showed cytoprotective activity in this system: (1) ligands at chloride channel receptors, such as glycine, strychnine and avermectin B1a; (2) chloride channel blockers, including cyanotriphenylboron and niflumic acid, both of which are known to bind to channel domains of CNS glycine receptors [27].

Gene context of niflumic acid

• Niflumic acid and MSI-2216 reduce TNF-alpha-induced mucin expression in human airway mucosa [28].
• To investigate how niflumic acid inhibits CFTR Cl(-) channel, we studied recombinant wild-type human CFTR in excised inside-out membrane patches [29].
• Thus, enhancement of the substrate-gated currents in EAAT4 does not correlate with the rate of substrate transport and suggests that the niflumic acid-induced currents are not thermodynamically coupled to the transport of substrate [30].
• In RPMA myocytes clamped at -60 mV, ET-1 induced an oscillatory inward current, the reversal potential of which was close to the equilibrium potential for Cl-. This current was unaltered by the removal of external Ca2+ but was abolished by niflumic acid (50 microM) [31].
• Moreover, niflumic acid (NFA), a blocker of hCLCA1-dependent Cl- efflux, inhibits MUC5A/C production in these cells [32].

Analytical, diagnostic and therapeutic context of niflumic acid

• Using the voltage-clamp technique on channels expressed in Xenopus laevis oocytes, we found that niflumic acid (NFA) increases CLC-Ka and CLC-Kb currents in the 10 to 1000 microM range [33].
• With a KCl microelectrode solution, all conductance increase which occurred in 190 mOsm PBS was inhibited by 200 microM niflumic acid, but not by 5 mM BaCl(2) [34].
• 6. Niflumic acid up to 100 microM, had neglible effects on either basal or stimulated (by 2 microM-(+/-)-isoprenaline) hormone secretion, as shown by radioimmunoassay of adrenocortotrophic hormone release.(ABSTRACT TRUNCATED AT 400 WORDS)[35]
• The aim of the present work was to investigate the separation of nonsteroidal anti-inflammatory drugs (NSAIDs: niflumic acid, flufenamic acid, piroxicam, alclofenac, tiaprofenic acid, flurbiprofen, suprofen, ketoprofen, naproxen, indomethacin, carprofen, indoprofen, sulindac) in capillary electrophoresis (CE) using completely nonaqueous systems [36].
• Our data suggest that the primary mechanism by which niflumic acid and NPPB inhibit pulmonary artery constriction is independent of Cl- channel blockade [37].

References