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Ozanimod, recently approved for treating relapsing MS, produced a disproportionate, active, MAO B-catalyzed metabolite (CC112273) that showed remarkable interspecies differences and led to challenges in safety testing. This study explored the kinetics of CC112273 formation from its precursor RP101075. Incubations with human liver mitochondrial fractions revealed KMapp, Vmax and Clint for CC112273 formation to be 4.8 mM, 50.3 pmol/min/mg protein and 12 ml/min/mg, respectively, while KM with human recombinant MAO B was 1.1 mM. Studies wi
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