1-OXAZOLO[4,5-B]PYRIDIN-2-YL-6-PHENYLHEXAN-1-ONE

Fatty acid amide hydrolase (FAAH) is the enzyme responsible for hydrolysis and inactivation of fatty acid amides including anandamide and oleamide. PHOP is a potent FAAH inhibitor, exhibiting Ki values of 0.094 nM and 0.2 nM for the human and rat enzymes, respectively. Using a proteomics approach, PHOP was screened against the serine hydrolase family of enzymes, of which FAAH is a member. In this assay, PHOP exhibited IC50 values of 1.1 nM, 1.4 nM, and >100 μM for FAAH, triacylglycerol hydrolase (TGH), and an uncharacterized hydrolase (KIAA1363), respectively. Knowledge of the specificity of PHOP obtained from this experiment should allow for more accurate interpretation of results using this inhibitor in complex environments such as whole cells or animals.