TY  - JOUR
A1  - Henderson, Colin J.
A1  - Mclaughlin, Lesley A.
A1  - Scheer, Nico
A1  - Stanley, Lesley A.
A1  - Wolf, C. Roland
T1  - Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s
JF  - Molecular Pharmacology
Y1  - 2015
U6  - http://dx.doi.org/10.1124/mol.114.097394
SN  - 1521-0111
VL  - 87
IS  - 4
SP  - 733
EP  - 739
PB  - ASPET
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Stanley, Lesley A.
A1  - Horsburgh, Brian C.
A1  - Ross, Jillian
A1  - Scheer, Nico
A1  - Wolf, C. Roland
T1  - Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior
JF  - Drug Metabolism Reviews
Y1  - 2009
U6  - http://dx.doi.org/10.1080/03602530802605040
SN  - 1097-9883
VL  - 41
IS  - 1
SP  - 27
EP  - 65
PB  - Taylor & Francis
CY  - London
ER  - 
TY  - JOUR
A1  - Stanley, Lesley A.
A1  - Horsburgh, Brian C.
A1  - Ross, Jillian
A1  - Scheer, Nico
A1  - Wolf, C. Roland
T1  - Nuclear Receptors which play a pivotal role in drug disposition and chemical toxicity
JF  - Drug Metabolism Reviews
Y1  - 2006
U6  - http://dx.doi.org/10.1080/03602530600786232
SN  - 1097-9883
VL  - 38
IS  - 3
SP  - 515
EP  - 597
ER  - 
TY  - JOUR
A1  - Scheer, Nico
A1  - Kapelyukh, Yury
A1  - McEwan, Jillian
A1  - Beuger, Vincent
A1  - Stanley, Lesley A.
A1  - Rode, Anja
A1  - Wolf, C. Roland
T1  - Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines
JF  - Molecular Pharmacology
N2  - The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine.
Y1  - 2012
U6  - http://dx.doi.org/10.1124/mol.111.075192
SN  - 1521-0111
VL  - 81
IS  - 1
SP  - 63
EP  - 72
PB  - ASPET
CY  - Bethesda, Md.
ER  -