Soluble epoxide hydrolase (sEH)

Class

Orally bioavailable, first-in-class soluble epoxide hydrolase (sEH) inhibitor (small molecule)

Pathway

Prevents sEH-mediated breakdown of epoxy fatty acids (EpFAs), prolonging their endogenous anti-inflammatory and analgesic activity

Soluble epoxide hydrolase (sEH) is an enzyme found in most tissues that breaks down a family of lipid signaling molecules called epoxy fatty acids (EpFAs), which are generated from arachidonic acid and other polyunsaturated fatty acids by cytochrome P450 enzymes. These EpFAs have naturally occurring anti-inflammatory, analgesic, and vascular-protective effects, but sEH rapidly converts them into less active diol metabolites, limiting how long their beneficial signaling persists. Inhibiting sEH slows this degradation, allowing EpFAs to accumulate and sustain their protective signaling for longer. This approach is of interest for conditions involving chronic pain, inflammation, and vascular dysfunction, because rather than introducing an external anti-inflammatory or analgesic agent, it amplifies an endogenous regulatory system already present in the body. Because the pathway is distinct from classical anti-inflammatory routes such as cyclooxygenase or opioid receptor signaling, sEH inhibition is explored as a mechanistically novel way to address pain and inflammation, potentially with a different tolerability profile than existing drug classes. Small molecule inhibitors occupy the enzyme's catalytic site, blocking its hydrolase activity. This mechanism is being studied across pain syndromes, inflammatory diseases, and cardiovascular or metabolic conditions where EpFA signaling is implicated.