Ecopladib (PLA 725) 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.

CPLA2α (GLU micelle):0.15 μM , CPLA2α (rat blood):0.11 μM

Ecopladib is inactive against COX-1 and COX-2 at a concentration of 20 μM, significantly higher than its IC50 in MC-9 cells. It effectively inhibits 12- and 15-HETE production through the 12- and 15-lipoxygenase pathways, with IC50 values around 0.3 μM. Furthermore, Ecopladib shows a 73% inhibition of cPLA2α at 37 nM in the PAPE liposome assay and a 16% inhibition of sPLA2 at 1 μM. It also suppresses the generation of prostaglandins (PGF2α) and leukotrienes (LTB4 and LTC4/D4/E4), with IC50 values ranging between 20−30 nM, demonstrating its effectiveness across multiple pathways involved in inflammation and cell signaling.

Ecopladib is orally efficacious at reducing carrageenan-induced paw swelling: from dose−response studies, it is determined that the ED50 is 40 mg/kg.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[1].