tcsc4811 Flufenamic acid

Flufenamic acid is a non-steroidal anti-inflammatory agent, inhibits cyclooxygenase (COX), activates AMPK, and also modulates ion channels, blocking chloride channels and L-type Ca²⁺ channels, modulating non-selective cation channels (NSC), activating K⁺ channels.

IC50 & Target: COX, Chloride Channel, Calcium Channel, Potassium Channel^[1], AMPK^[2]

In Vitro: Flufenamic acid is a non-steroidal anti-inflammatory agent, inhibits cyclooxygenase (COX), and also modulates ion channels, blocking chloride channels and L-type Ca²⁺ channels, modulating non-selective cation channels (NSC), activating K⁺ channels. Flufenamic acid inhibits a wide spectrum of TRP channels, including: C3, C7, M2, M3, M4, M5, M7, M8, V1, V3, and V4 but activates at least two TRP channels (C6 and A1)^[1]. Flufenamic acid induces AMPK activation in T84 cells, and such an effect is via a direct stimulation of calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ) activity^[2]. Moreover, Flufenamic acid (FFA; 5-50 μM) dose-dependently inhibits cAMP-dependent Cl^- secretion in intact T84 cells, suppresses CFTR-mediated apical I_Cl^-, and blocks the Ca²⁺-dependent Cl^- secretion in a dose-dependent manner with IC₅₀ of appr 10 μM and near complete inhibition at 100 μM in T84 cell monolayers, but shows no effect on Na⁺-K⁺ ATPase or NKCC in T84 cells^[3].

In Vivo: Flufenamic acid (50 mg/kg, i.p.) has anti-inflammatory effect in a mouse model of Vibrio cholerae El Tor variant (EL)-induced diarrhea and significantly abrogates EL-induced intestinal fluid secretion and barrier disruption at 20 mg/kg. Furthermore, Flufenamic acid suppresses NF-κB nuclear translocation and expression of proinflammatory mediators and promotes AMPK phosphorylation in the EL-infected mouse intestine^[2].