Shandan Qu, Guangxuan Liu
Jun 23, 2021
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Journal
Rapid communications in mass spectrometry : RCM
Abstract
RATIONALES Daporinad is a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed to explore the metabolites of daporinad generated from liver microsomes and to propose metabolic pathways. METHODS The metabolites were generated by individually incubating daporinad (10 μM) with liver microsomes at 37 o C for 60 min. The metabolites were identified by ultra-high performance liquid chromatography-quadrupole/orbitrap mass spectrometer (UPLC-Q/Orbitrap-MS) using electrospray ionization in positive ion mode. They were deduced by accurate MS and MS/MS data. RESULTS Totally, sixteen metabolites were found and their identities were characterized. In rat, dog and human, they were minor; in monkey, M11 was the most. Daporinad was metabolized mainly through N-dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. There was human-specific metabolite. CONCLUSIONS The current study provided an overview of the metabolism of daporinad, which is helpful in predicting in vivo metabolites and in selecting animal species for toxic study.