The molecular mechanism of human hormone-sensitive lipase inhibition by substituted 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-ones

► The specific inhibition of hormone-sensitive lipase (HSL) by oxadiazolones was studied. ► The IC50 of compound 7600 and compound 9368 was found to be around 250 nM and 90 nM, respectively. ► The HSL inhibition is reversed in the presence of lipid substrate. ► The mechanism of the reversible inhibition of HSL by compound 7600 was investigated using LC-MS.