“Phase I metabolism is not just about CYPs,” says Dr. Julia Shanu-Wilson of Hypha Discovery. “An impressive range of reactions are catalyzed by a number of enzymes, and this article is a useful reminder of this.”
“Biotransformation “networks” also result in impressive examples such as seen in the metabolism of ozanimod where no single enzyme system predominates. In fact, ozanimod is metabolised by phase 1 reactions that not only include multiple CYPs, but also ADH/ALDH, MAO-B and CBR, as well as ring opening and scission by gut microflora. There’s also phase 2 metabolism at play featuring NAT2 and UGTs. Active metabolites also result from biotransformation of ozanimod where, for instance, a long-lived MAO-B metabolite of a CYP metabolite is also an active metabolite.”
“An understanding of the biotransformation of a drug provides opportunity not only for addressing any safety concerns but also provides an opportunity for SAR and unearthing metabolites with interesting properties distinct from those displayed by the parent drug.”
Hypha Discovery is a specialist CRO supporting pharma companies worldwide through production, purification and identification of metabolites and late-stage drug derivatives.
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