Biological Activity
Flufenamic acid-d4 is intended for use as an internal standard for the quantification of flufenamic acid by GC- or LC-MS. Flufenamic acid is a non-steroidal anti-inflammatory drug (NSAID) and COX inhibitor (IC50s = 3 and 9.3 μM for human COX-1 and COX-2, respectively).1 Flufenamic acid inhibits TNF-α-induced increases in COX-2 levels and NF-κB activation in HT-29 colon cancer cells in a concentration-dependent manner.2 It inhibits calcium influx induced by fMLP or A23187 in human polymorphonuclear leukocytes (PMN) with IC50 values of 29 and 14 μM, respectively.3 Flufenamic acid also activates various ion channels, including transient receptor potential canonical 6 (TRPC6) and the large-conductance calcium-activated potassium channel (KCa1.1).4 It also inhibits various ion channels, including TRPC3 and the cystic fibrosis transmembrane conductance regulator (CFTR). Flufenamic acid (20 mg/kg) reduces increases in intestinal fluid secretion and intestinal barrier disruption in mice infected with the El Tor variant of V. cholerae.5
References
1.Warner, T.D., Giuliano, F., Vojnovic, I., et al.Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: A full in vitro analysisProc. Nat. Acad. Sci. USA96(13)7563-7568(1999)
2.Paik, J.H., Ju, J.H., Lee, J.Y., et al.Two opposing effects of non-steroidal anti-inflammatory drugs on the expression of the inducible cyclooxygenase. Mediation through different signaling pathwaysJ. Biol. Chem.275(36)28173-28179(2000)
3.Kankaanranta, H., and Moilanen, E.Flufenamic and tolfenamic acids inhibit calcium influx in human polymorphonuclear leukocytesMol. Pharmacol.47(5)1006-1013(1995)
4.Guinamard, R., Simard, C., and Del Negro, C.Flufenamic acid as an ion channel modulatorPharmacol. Ther.138(2)272-284(2013)
5.Pongkorpsakol, P., Satitsri, S., Wongkrasant, P., et al.Flufenamic acid protects against intestinal fluid secretion and barrier leakage in a mouse model of Vibrio cholerae infection through NF-κB inhibition and AMPK activationEur. J. Pharmacol.79894-104(2017)
