Ecopladib

Ecopladib is a sub-micromolar inhibitor of cytosolic phospholipase A2α (cPLA2α), with IC₅₀s of 0.15 μM and 0.11 μM in the GLU micelle and rat whole blood assays, respectively. IC50 & Target: IC50: 0.15 μM (cPLA2α, in GLU micelle), 0.11 μM (cPLA2α, rat blood)^[1] In Vitro: Ecopladib inhibits cPLA2α in the PAPE liposome assay at 73% at a concentration of 37 nM, while it inhibits sPLA2 at 16% at 1 μM. Ecopladib inhibits the production of prostaglandins (PGF2α) and leukotrienes (LTB4 and LTC4/D4/E4) with comparable IC₅₀s of 20?30 nM. Ecopladib is inactive against COX-1 and COX-2 at 20 μM, which is nearly 100 times the IC₅₀ in the MC-9 cells. Ecopladib inhibit 12- and 15-HETE, which are derived from arachidonic acid via the 12- and 15-lipoxygenase pathways and the IC₅₀s are ～0.3 μM^[1]. In Vivo: Ecopladib is orally efficacious in this model and displays an ED₅₀ of 8 mg/kg, demonstrating that it can inhibit COX-2 derived PGE2 formation in vivo. Ecopladib is orally efficacious at reducing carrageenan-induced paw swelling:?from dose?response studies, it is determined that the ED₅₀ is 40 mg/kg^[1].