Flufenamic Acid-d4 (Synonyms: FFA-d4, Fluphenamic Acid-d4)

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 (K_Ca1.1).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

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)