A broad-spectrum substrate for the human UDP-glucuronosyltransferases and its use for investigating glucuronidation inhibitors

Strong inhibition of the human UDP-glucuronosyltransferase enzymes (UGTs) may lead to undesirable effects, including hyperbilirubinaemia and drug/herb-drug interactions. Currently, there is no good way examine inhibitory effects specificities compounds toward all important UGTs, side-by-side under identical conditions. Herein, we report a new, broad-spectrum substrate for UGTs its uses in screening characterizing UGT inhibitors. Following variety phenolic compound(s), have found that methylophiopogonanone A (MOA) can be readily O -glucuronidated by tested typical N -glucuronidating UGT1A4 UGT2B10. MOA- -glucuronidation yielded single mono- -glucuronide was biosynthesized purified structural characterization constructing an LC-UV based activity assay, which then used investigating kinetics recombinant UGTs. The derived K m values were crucial selecting most suitable assay conditions assessing potentials specificity test compound(s). Furthermore, four known inhibitors reinvestigated using MOA as Collectively, offers new practical tool • broad with activity. 13 investigated. An developed substrate.