TPPU

TPPU is a soluble epoxide hydrolase (sEH) inhibitor with IC₅₀ values of 37 and 3.7 nM for monkey and human sEH, respectively. IC50 & Target:IC50: 37 nM (Monkey sEH), 3.7 nM (Human sEH)^[1] In Vitro:Soluble epoxide hydrolase inhibitors (sEHIs) possess anti-inflammatory, antiatherosclerotic, antihypertensive and analgesic properties^[1]. In the Caco-2 cells permeability assay, TPPU rapidly passes the cell monolayer, suggesting it will have a good intestinal permeability^[2]. In Vivo:TPPU is suitable for investigating soluble epoxide hydrolase biology and the role of epoxide-containing lipids in modulating inflammatory diseases. TPPU displays high plasma concentrations when dosed orally at 0.3 mg/kg and drug-like properties. The C_max increases with dose from 0.3 to 3 mg/kg for TPPU^[1]. Following administration in drinking water to rats (0.2, 1, and 5 mg TPPU/L with 0.2% PEG400), TPPU’s blood concentration increases dose dependently within the treatment period to reach an almost steady state after 8 days^[2]. The sEH inhibitor, TPPU, shows antidepressant effects in animal models of depression. Expression of sEH protein is increased in the brain of chronically stressed mice and depressed patients. Prophylactic sEH inhibition or sEH-KO results in resilience to repeated social defeat stress, associated with increased BDNF-TrkB signaling in prefrontal cortex and hippocampus of KO mice^[3].