In vitro activity: GSK2256294A (also known as GSK2256294) is a novel, potent, selective inhibitor of recombinant human, rat and mouse sEH (Soluble epoxide hydrolase) with IC50 of 27 pM. It also displays potent inhibition against the rat (IC50 = 61 pM) and murine (IC50 = 189 pM) orthologs of sEH. GSK2256294A, exhibited potent cell-based activity, a concentration-dependent inhibition of the conversion of 14,15-EET to 14,15-DHET in human, rat and mouse whole blood in vitro, and a dose-dependent increase in the LTX/LTX diol ratio in rat plasma following oral administration. Mice receiving 10 days of cigarette smoke exposure concomitant with oral administration of GSK2256294A exhibited significant, dose-dependent reductions in pulmonary leukocytes and keratinocyte chemoattractant (KC, CXCL1) levels. Mice receiving oral administration of GSK2256294A following 10 days of cigarette smoke exposure exhibited significant reductions in pulmonary leukocytes compared to vehicle-treated mice. These data indicate that GSK2256294A attenuates cigarette smoke-induced inflammation by both inhibiting its initiation and/or maintenance and promoting its resolution. Collectively, these data indicate that GSK2256294A would be an appropriate agent to evaluate the role of sEH in clinical studies, for example in diseases where cigarette smoke is a risk factor, such as chronic obstructive pulmonary disease (COPD) and cardiovascular disease.

Kinase Assay: GSK2256294A (also known as GSK2256294) is a novel, potent, selective inhibitor of recombinant human, rat and mouse sEH (Soluble epoxide hydrolase) with IC50 of 27 pM. It also displays potent inhibition against the rat (IC50 = 61 pM) and murine (IC50 = 189 pM) orthologs of sEH.

Cell Assay: GSK2256294A also displays potent cellular inhibition (IC50 = 0.66 nM) of sEH in an assay developed using a cell line transfected with the human sEH enzyme.