Tamoxifen remains a cornerstone of treatment for patients with oestrogen-receptor-positive breast cancer. Tamoxifen efficacy depends on the biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoform, to the active metabolite endoxifen. Both genetic and environmental (drug-induced) factors may alter CYP2D6 enzyme activity directly affecting the concentrations of active tamoxif...

The CYP2D6 gene is responsible for metabolising a large portion of the commonly prescribed drugs. Because of its importance, various approaches have been taken to analyse CYP2D6 and Single Nucleotide Polymorphisms (SNPs) throughout its sequence. This study introduces a novel method to analyse the effects of SNPs on encoded protein complexes by focusing on the biochemical properties of each non-...

TaqMan™ genotyping assays are widely used to genotype CYP2D6, which encodes a major drug metabolizing enzyme. Assay design for CYP2D6 can be challenging owing to the presence of two pseudogenes, CYP2D7 and CYP2D8, structural and copy number variation and numerous single nucleotide polymorphisms (SNPs) some of which reflect the wild-type sequence of the CYP2D7 pseudogene. The aim of this study w...

Cytochrome P450 2D6 (CYP2D6) is among the most important genes involved in drug metabolism. Specific variants are associated with changes in the enzyme's amount and activity. Multiple technologies exist to determine these variants, like the AmpliChip CYP450 test, Taqman qPCR, or Second-Generation Sequencing, however, sequence homology between cytochrome P450 genes and pseudogene CYP2D7 impairs ...

Patients with cancer often take many different classes of drugs to treat the effects of their malignancy and the side effects of treatment, as well as their comorbidities. The potential for drug-drug interactions that may affect the efficacy of anticancer treatment is high, and a major source of such interactions is competition for the drug-metabolizing enzymes, cytochromes P450 (P450s). We hav...

Diphenhydramine is widely used as an over-the-counter antihistamine. However, the specific human cytochrome P450 (P450) isozymes that mediate the metabolism of diphenhydramine in the range of clinically relevant concentrations (0.14-0.77 microM) remain unclear. Therefore, P450 isozymes involved in N-demethylation, a main metabolic pathway of diphenhydramine, were identified by a liquid chromato...

The gene CYP2D6 has an extremely important role in drug metabolism. "Cytochrome P450, family 2, subfamily D, polypeptide 6" is the official name of CYP2D6. The gene is located at position 13.1 on the long (q) arm of chromosome 21 and encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that are heavily involved in drug metabolism (Genet...

Flos carthami is a traditional Chinese herbal medicine. Clinically, the Flos carthami Injection has been used concomitantly with other Western drugs and may be used concomitantly with β-blockers, such as metoprolol, to treat cerebrovascular and coronary heart diseases, in China. Metoprolol is a CYP2D6 substrate and is predominantly metabolized by this isozyme. However, we do not know whether th...

Microsomal cytochrome P450 monooxygenases of groups 1-3 are mainly expressed in the liver and play a crucial role in phase 1 reactions of xenobiotic metabolism. The cDNAs encoding human CYP2D6 and human NADPH-P450 oxidoreductase (CPR) were transformed into the methylotrophic yeast Pichia pastoris and expressed with control of the methanol-inducible AOX1 promoter. The determined molecular weight...

Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of estrogen receptor positive (ER(+)) mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6). It is widely accepted that CYP2D6 poor metabolizers exert a pron...