sEH/FLAP-IN-2 is a selective dual inhibitor of sEH (IC50 = 12.6 nM) and FLAP. It significantly reduces lipids derived from 5-LOX/FLAP and sEH, thereby promoting the redistribution of these lipids. sEH/FLAP-IN-2 is applicable in peritonitis research.

sEH/FLAP-IN-2 (Compound 6) does not exhibit significant inhibitory activity against 5-LOX, with an IC₅₀ value greater than 10 μM. In human neutrophils, at a concentration of 10 μM for 15 minutes, it significantly reduces the production of 5-LOX products (LTB4, trans-LTB4, and 5-HETE) in a FLAP-dependent system without exogenous arachidonic acid (AA), achieving a residual activity of 35.7%. However, its inhibitory effect diminishes in the presence of exogenous AA (IC₅₀ > 10 μM). The compound (0.1-10 μM, 16 minutes) does not significantly affect the activity of COX-1, COX-2, and mPGES-1. Furthermore, sEH/FLAP-IN-2 (0.1-10 μM, 120 minutes) inhibits 5-LOX/FLAP-derived mediators (such as LTB4 and LTC4) in a concentration-dependent manner, particularly in M1-MDM, while increasing COX-derived prostaglandins (such as PGE2 and PGD2) without affecting the levels of SPMs (such as RvD5).

sEH/FLAP-IN-2 (Compound 6) (10 mg/kg, intraperitoneal injection, single dose) effectively modulates the lipid mediator profile in a mouse peritonitis model by dual inhibition of FLAP and sEH, shifting it from a pro-inflammatory state (LTs and DHETs) to an anti-inflammatory state (EETs).