Abstract
Owing to the polymorphic nature of CYP2D6, clinically significant issues can arise when drugs rely on that enzyme either for clearance, or metabolism to an active metabolite. Available screening methods to determine if the compound is likely to cause drug-drug interactions, or is likely to be a victim of inhibition of CYP2D6 by other compounds will be described. Computational models and examples will be given on strategies to design out the CYP2D6 liabilities for both heme-binding compounds and non-heme-binding compounds.
MeSH terms
-
Animals
-
Biotransformation
-
Computer Simulation
-
Computer-Aided Design
-
Cytochrome P-450 CYP2D6 / chemistry
-
Cytochrome P-450 CYP2D6 / genetics
-
Cytochrome P-450 CYP2D6 / metabolism*
-
Cytochrome P-450 CYP2D6 Inhibitors
-
Drug Design
-
Drug Interactions*
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology*
-
Heme / metabolism
-
Humans
-
Models, Molecular
-
Molecular Structure
-
Protein Conformation
-
Quantitative Structure-Activity Relationship
-
Risk Assessment
-
Substrate Specificity
Substances
-
Cytochrome P-450 CYP2D6 Inhibitors
-
Enzyme Inhibitors
-
Heme
-
Cytochrome P-450 CYP2D6