Researchers at the University of California, Davis have developed compounds that concurrently inhibit Soluble Epoxide Hydrolase (sEH) and Fatty Acid Amide Hydrolase (FAAH as therapeutics for treating pain. sEH and FAAH inhibition have been independently developed as pharmaceutical targets for treating inflammatory and neuropathic pain but concurrent inhibition of these two targets is synergistic and combining of both targets into a single therapeutic approach may provide better pain relief for patients.
Soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH) regulate inflammation, pain and other biological processes relevant to human health. Their biological activities are mediated by their substrates epoxyeicosatrienoic acid (EET) and arachidonoyl ethanolamide (AEA), respectively, and are essential components of eicosanoid and endocannabinoid signaling, respectively. These signaling pathways are known to modulate a number of disease states, including chronic pain, hypertension and cancer, and thus, these two enzymes are promising clinical targets.
Despite substantial promising pre-clinical data for both sEH and FAAH inhibitors, none of the clinical trials to date have demonstrated efficacy for either target. One approach to overcoming this obstacle is to target two or more parallel pathways involved in the same disease. To harness this synergy while simplifying pharmacokinetics, researchers at the University of California, Davis have developed dual inhibitors that concurrently inhibit these two targets. These dual inhibitors may be applied as powerful therapeutics and are useful experimental tools for identifying other indications where sEH/FAAH synergy may be used therapeutically.