Cytochrome P450 family 3 subfamily A (CYP3A) (CYP3A)

Cytochrome P450 family 3 subfamily A (CYP3A) is a group of heme-thiolate monooxygenases, including the prominent CYP3A4 and CYP3A5 isoforms, which are primarily located in the liver and small intestine (UniProt P08684). These enzymes are responsible for the oxidative metabolism of a vast majority of therapeutic drugs, including the WEE1 kinase inhibitor adavosertib (PubMed 28631285). Adavosertib is a sensitive substrate of CYP3A, meaning its clearance and systemic exposure are heavily dependent on the activity of these enzymes (PubMed 30109725). Co-administration of adavosertib with strong CYP3A inhibitors can lead to toxic plasma levels, while co-administration with inducers can result in sub-therapeutic concentrations (PubMed 28631285). Consequently, the CYP3A-mediated metabolism of adavosertib is a critical factor in clinical trial design and patient safety management (NIH/NCI).

Other names

CYP3A4CYP3A5Cytochrome P450 3ANifedipine oxidaseSteroid hydroxylaseHLPP450PCN1

CYP3A enzymes catalyze the oxidative metabolism of adavosertib, primarily through O-desmethylation and N-dealkylation, which facilitates the clearance of the drug from the systemic circulation (PubMed 28631285).