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Chemical Compound Review

Donalgin     2-[[3-(trifluoromethyl) phenyl]amino]pyridi...

Synonyms: Niflugel, Nifluril, Niflactol, Flunir, niflumic acid, ...
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Disease relevance of niflumic acid


High impact information on niflumic acid


Chemical compound and disease context of niflumic acid


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


Associations of niflumic acid with other chemical compounds


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


  1. Niflumic acid suppresses interleukin-13-induced asthma phenotypes. Nakano, T., Inoue, H., Fukuyama, S., Matsumoto, K., Matsumura, M., Tsuda, M., Matsumoto, T., Aizawa, H., Nakanishi, Y. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  2. Ca2+ current and Ca(2+)-activated chloride current in isolated smooth muscle cells of the sheep urethra. Cotton, K.D., Hollywood, M.A., McHale, N.G., Thornbury, K.D. J. Physiol. (Lond.) (1997) [Pubmed]
  3. Short-term niflumic-acid-induced acute renal failure in children. Lantz, B., Cochat, P., Bouchet, J.L., Fischbach, M. Nephrol. Dial. Transplant. (1994) [Pubmed]
  4. Effects of chloride flux modulators in an in vitro model of brain edema formation. Kumar, V., Naik, R.S., Hillert, M., Klein, J. Brain Res. (2006) [Pubmed]
  5. Nonsteroidal anti-inflammatory drugs differentially affect the heat shock response in cultured spinal cord cells. Batulan, Z., Nalbantoglu, J., Durham, H.D. Cell Stress Chaperones (2005) [Pubmed]
  6. Speract induces calcium oscillations in the sperm tail. Wood, C.D., Darszon, A., Whitaker, M. J. Cell Biol. (2003) [Pubmed]
  7. Identification and modulation of a voltage-dependent anion channel in the plasma membrane of guard cells by high-affinity ligands. Marten, I., Zeilinger, C., Redhead, C., Landry, D.W., al-Awqati, Q., Hedrich, R. EMBO J. (1992) [Pubmed]
  8. Calcium-activated chloride current in rabbit coronary artery myocytes. Lamb, F.S., Volk, K.A., Shibata, E.F. Circ. Res. (1994) [Pubmed]
  9. Anion Channels, Including ClC-3, Are Required for Normal Neutrophil Oxidative Function, Phagocytosis, and Transendothelial Migration. Moreland, J.G., Davis, A.P., Bailey, G., Nauseef, W.M., Lamb, F.S. J. Biol. Chem. (2006) [Pubmed]
  10. Molecular and functional analyses of two new calcium-activated chloride channel family members from mouse eye and intestine. Evans, S.R., Thoreson, W.B., Beck, C.L. J. Biol. Chem. (2004) [Pubmed]
  11. The effects of TNF-alpha and inhibitors of arachidonic acid metabolism on human colon HT-29 cells depend on differentiation status. Kovaríková, M., Hofmanová, J., Soucek, K., Kozubík, A. Differentiation (2004) [Pubmed]
  12. Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression. Larkins, T.L., Nowell, M., Singh, S., Sanford, G.L. BMC Cancer (2006) [Pubmed]
  13. Effects of human low-density lipoproteins on superoxide production by formyl-methionyl-leucyl-phenylalanine activated polymorphonuclear leukocytes. Bonneau, C., Couderc, R., Tissot, M., Athias, A., Roch-Arveiller, M., Giroud, J.P. European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies. (1997) [Pubmed]
  14. Blockade of capacitive Ca2+ influx by Cl- channel blockers inhibits secretion from rat mucosal-type mast cells. Reinsprecht, M., Rohn, M.H., Spadinger, R.J., Pecht, I., Schindler, H., Romanin, C. Mol. Pharmacol. (1995) [Pubmed]
  15. Role of chloride channels in bradykinin-induced guinea pig airway vagal C-fibre activation. Lee, M.G., Macglashan, D.W., Undem, B.J. J. Physiol. (Lond.) (2005) [Pubmed]
  16. Altered properties of volume-sensitive osmolyte and anion channels (VSOACs) and membrane protein expression in cardiac and smooth muscle myocytes from Clcn3-/- mice. Yamamoto-Mizuma, S., Wang, G.X., Liu, L.L., Schegg, K., Hatton, W.J., Duan, D., Horowitz, T.L., Lamb, F.S., Hume, J.R. J. Physiol. (Lond.) (2004) [Pubmed]
  17. Functional role of sodium-calcium exchange in the regulation of renal vascular resistance. Schweda, F., Seebauer, H., Krämer, B.K., Kurtz, A. Am. J. Physiol. Renal Physiol. (2001) [Pubmed]
  18. Functional geometry of the permeation pathway of Ca2+-activated Cl-channels inferred from analysis of voltage-dependent block. Qu, Z., Hartzell, H.C. J. Biol. Chem. (2001) [Pubmed]
  19. Characterization of the enhanced transport of L- and D-lactate into human red blood cells infected with Plasmodium falciparum suggests the presence of a novel saturable lactate proton cotransporter. Cranmer, S.L., Conant, A.R., Gutteridge, W.E., Halestrap, A.P. J. Biol. Chem. (1995) [Pubmed]
  20. The kinetics, substrate, and inhibitor specificity of the monocarboxylate (lactate) transporter of rat liver cells determined using the fluorescent intracellular pH indicator, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Jackson, V.N., Halestrap, A.P. J. Biol. Chem. (1996) [Pubmed]
  21. Cyclooxygenase-2 (PTGS2) inhibitors augment the rate of hexose transport in L6 myotubes in an insulin- and AMPKalpha-independent manner. Alpert, E., Gruzman, A., Lardi-Studler, B., Cohen, G., Reich, R., Sasson, S. Diabetologia (2006) [Pubmed]
  22. Dynamics of Ca2+-dependent Cl- channel modulation by niflumic acid in rabbit coronary arterial myocytes. Ledoux, J., Greenwood, I.A., Leblanc, N. Mol. Pharmacol. (2005) [Pubmed]
  23. The DC electrical-field-induced Ca(2+) response and growth stimulation of multicellular tumor spheroids are mediated by ATP release and purinergic receptor stimulation. Sauer, H., Stanelle, R., Hescheler, J., Wartenberg, M. J. Cell. Sci. (2002) [Pubmed]
  24. Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes. White, M.M., Aylwin, M. Mol. Pharmacol. (1990) [Pubmed]
  25. Stimulation of Ca(2+)-dependent membrane currents in Xenopus oocytes by microinjection of pyrimidine nucleotide-glucose conjugates. Kim, H.Y., Thomas, D., Hanley, M.R. Mol. Pharmacol. (1996) [Pubmed]
  26. Haptoglobin release by human adipose tissue in primary culture. Fain, J.N., Bahouth, S.W., Madan, A.K. J. Lipid Res. (2004) [Pubmed]
  27. Cytoprotection of kidney epithelial cells by compounds that target amino acid gated chloride channels. Venkatachalam, M.A., Weinberg, J.M., Patel, Y., Saikumar, P., Dong, Z. Kidney Int. (1996) [Pubmed]
  28. Niflumic acid and MSI-2216 reduce TNF-alpha-induced mucin expression in human airway mucosa. Hauber, H.P., Daigneault, P., Frenkiel, S., Lavigne, F., Hung, H.L., Levitt, R.C., Hamid, Q. J. Allergy Clin. Immunol. (2005) [Pubmed]
  29. Direct block of the cystic fibrosis transmembrane conductance regulator Cl(-) channel by niflumic acid. Scott-Ward Section Sign, T.S., Li Section Sign, H., Schmidt, A., Cai, Z., Sheppard, D.N. Mol. Membr. Biol. (2004) [Pubmed]
  30. Niflumic acid modulates uncoupled substrate-gated conductances in the human glutamate transporter EAAT4. Poulsen, M.V., Vandenberg, R.J. J. Physiol. (Lond.) (2001) [Pubmed]
  31. Cellular mechanisms and role of endothelin-1-induced calcium oscillations in pulmonary arterial myocytes. Hyvelin, J.M., Guibert, C., Marthan, R., Savineau, J.P. Am. J. Physiol. (1998) [Pubmed]
  32. A calcium-activated chloride channel blocker inhibits goblet cell metaplasia and mucus overproduction. Zhou, Y., Shapiro, M., Dong, Q., Louahed, J., Weiss, C., Wan, S., Chen, Q., Dragwa, C., Savio, D., Huang, M., Fuller, C., Tomer, Y., Nicolaides, N.C., McLane, M., Levitt, R.C. Novartis Found. Symp. (2002) [Pubmed]
  33. Activation and inhibition of kidney CLC-K chloride channels by fenamates. Liantonio, A., Picollo, A., Babini, E., Carbonara, G., Fracchiolla, G., Loiodice, F., Tortorella, V., Pusch, M., Camerino, D.C. Mol. Pharmacol. (2006) [Pubmed]
  34. Increased potassium, chloride, and taurine conductances in astrocytes during hypoosmotic swelling. Olson, J.E., Li, G.Z. Glia (1997) [Pubmed]
  35. Control of action potentials and Ca2+ influx by the Ca(2+)-dependent chloride current in mouse pituitary cells. Korn, S.J., Bolden, A., Horn, R. J. Physiol. (Lond.) (1991) [Pubmed]
  36. Separation of nonsteroidal anti-inflammatory drugs by capillary electrophoresis using nonaqueous electrolytes. Fillet, M., Bechet, I., Piette, V., Crommen, J. Electrophoresis (1999) [Pubmed]
  37. Relaxation of endothelin-1-induced pulmonary arterial constriction by niflumic acid and NPPB: mechanism(s) independent of chloride channel block. Kato, K., Evans, A.M., Kozlowski, R.Z. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
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