330597-62-1

Basic information

• Product Name: Cytochrome P450 2D6
• Synonyms: CYP2D6;CYPIID6;Debrisoquine 4-hydroxylase;P450-DB1;Cytochrome P450 2D6;Anti-Cytochrome P450 2D6 antibody produced in rabbit
• CAS NO: 330597-62-1
• Molecular Formula: C37H40FeN5O7S
• Molecular Weight: 754.6528
• Product Categories: Human P450 Cytochromes
• Mol File: 330597-62-1.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Storage Temp.: -20°C
• CAS DataBase Reference: Cytochrome P450 2D6(CAS DataBase Reference)
• NIST Chemistry Reference: Cytochrome P450 2D6(330597-62-1)
• EPA Substance Registry System: Cytochrome P450 2D6(330597-62-1)

Safety Data

• Hazardous Substances Data: 330597-62-1(Hazardous Substances Data)

Usage

Description

Cytochrome P450 2D6 (CYP2D6) is a crucial enzyme involved in the metabolism of a wide range of commonly prescribed drugs, including antidepressants, antipsychotics, β-adrenergic blockers, and antiarrhythmics. CYP2D6 deficiency is a clinically important genetic variation of drug metabolism, characterized by three phenotypes: ultra-rapid metabolizers (UM), extensive metabolizers (EM), and poor metabolizers (PM). The PM phenotype is inherited as an autosomal recessive trait, with certain gene mutations leading to either zero expression or the expression of a nonfunctional enzyme.
Used in Pharmaceutical Industry:
Cytochrome P450 2D6 is used as a drug-metabolizing enzyme for the metabolism of various commonly prescribed medications. Understanding the genetic variations in CYP2D6 expression and function is essential for personalized medicine, as it helps in determining the appropriate dosage and potential drug interactions for individuals with different phenotypes.
Cytochrome P450 2D6 is used as a biomarker for identifying individuals with different metabolic phenotypes (UM, EM, and PM) to predict their response to specific medications and potential adverse effects or drug toxicity.
Used in Research and Development:
Cytochrome P450 2D6 is used as a target for studying the genetic variations and their impact on drug metabolism, which aids in the development of new drugs and drug delivery systems that can overcome the limitations of individuals with different CYP2D6 phenotypes.
Used in Drug Interaction Studies:
Cytochrome P450 2D6 is used as a factor in evaluating drug-drug interactions, as its activity can be influenced by other medications, leading to altered drug metabolism and potential adverse effects.
Used in Toxicology Studies:
Cytochrome P450 2D6 is used as a determinant of drug toxicity, as individuals with different CYP2D6 phenotypes may be predisposed to adverse effects or drug toxicity due to inadequate metabolism or long half-lives of certain medications.

Clinical Use

The CYP2D6 polymorphism is, perhaps, the most studied CYP450. This enzyme is responsible for at least 30 different drug oxidations, representing approximately 21% of the clinically important drugs. The CYP2D6 is only 3% expressed in the liver and minimally expressed in the intestine, and it does not appear to be inducible. Because there may be no other way to clear drugs metabolized by CYP2D6 from the system, poor metabolizers of CYP2D6 substrates may be at severe risk for adverse drug reactions or drug overdose. The metabolism of debrisoquine by CYP2D6 is one of the most studied examples of metabolic polymorphism, with its molecular basis of defective metabolism being well understood. This isoform metabolizes a wide variety of lipophilic amines and is probably the only CYP450 for which a charged or ion-pair interaction is important for substrate binding. It also appears to preferentially catalyze the hydroxylation of a single enantiomer (stereoselectivity) in the presence of enantiomeric mixtures. Quinidine is an inhibitor of CYP2D6, and concurrent administration with CYP2D6 substrates results in increased blood levels and toxicity for these substrates. If the pharmacological action of the CYP2D6 substrate depends on the formation of active metabolites, quinidine inhibition results in a lack of a therapeutic response. The interaction of two substrates for CYP2D6 can prompt a number of clinical responses. For example, depending on which substrate has the greater affinity for CYP2D6, the first-pass hepatic metabolism of the substrate (drug) with weaker affinity will be inhibited by a second substrate having greater affinity. The result of this will be a decrease and prolongation of elimination of the first substrate, leading to a higher plasma concentration and an increased potential for adverse toxicity.