Cytochrome P450 family 3 subfamily A member 2 (CYP3A2) (CYP3A2)

Cytochrome P450 3A2 (CYP3A2) is a major hepatic enzyme in rats, belonging to the cytochrome P450 superfamily and serving as the functional ortholog to the human CYP3A4 enzyme (UniProt: P05183). It plays a pivotal role in the oxidative metabolism of a wide variety of exogenous compounds, including over 50% of clinically prescribed drugs, and endogenous steroids like testosterone. Dihydrotanshinone I is a bioactive diterpene quinone derived from the traditional Chinese medicinal herb Salvia miltiorrhiza, also known as Danshen (PubChem CID: 114130). Research has identified dihydrotanshinone I as a potent inhibitor of CYP3A2, functioning through both competitive inhibition and mechanism-based inactivation, which leads to the irreversible loss of enzyme function (PMID: 20633569). This interaction is of significant pharmacological interest because the inhibition of CYP3A2 can drastically reduce the clearance of co-administered drugs, leading to increased systemic exposure and potential toxicity (PubMed: 21114907). Consequently, CYP3A2 is a critical focus in preclinical studies for evaluating herb-drug interactions and ensuring the safety of multi-drug regimens. Understanding the modulation of this enzyme by natural products like dihydrotanshinone I is essential for predicting metabolic drug-drug interactions in animal models.

Other names

Cytochrome P450 3A2Cytochrome P450-PCN2P450-PCN2Testosterone 6-beta-hydroxylaseCYPIIIA2

The enzyme catalyzes the oxidative metabolism of substrates; Dihydrotanshinone I acts as a potent inhibitor and mechanism-based inactivator of this catalytic activity (PMID: 20633569).