Rationale: Daporinad is really a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed look around the metabolites of daporinad produced by liver microsomes and also to propose metabolic pathways.
Methods: The metabolites were generated by individually incubating daporinad (10 |ìM) with liver microsomes at 37??C for 60 min. The metabolites were recognized by ultra-high-performance liquid chromatography/quadrupole-orbitrap mass spectrometry (UPLC/Q-Orbitrap-MS) using electrospray ion technology in positive ion mode. These were deduced by accurate MS and MS/MS data.
Results: As a whole, 16 metabolites put together as well as their identities were characterised. In rat, dog and human, these were minor in monkey, M11 was probably the most abundant. Daporinad was metabolized mainly through N-dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. There wasn’t any human-specific metabolite.
Conclusions: The present study provided an introduction to the metabolic process of daporinad, that is useful in predicting in vivo metabolites as well as in selecting animal species for toxicology studies.