Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line
M Hasegawa, Y Kapelyukh, H Tahara, J Seibler… - Molecular …, 2011 - ASPET
Cytochrome P450 (P450) 3A4 is the predominant P450 enzyme expressed in human liver
and intestine, and it is involved in the metabolism of approximately 50% of clinically used …
and intestine, and it is involved in the metabolism of approximately 50% of clinically used …
Defining the contribution of CYP1A1 and CYP1A2 to drug metabolism using humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 knockout mice
Y Kapelyukh, CJ Henderson, N Scheer, A Rode… - Drug Metabolism and …, 2019 - ASPET
Cytochrome P450s CYP1A1 and CYP1A2 can metabolize a broad range of foreign compounds
and drugs. However, these enzymes have significantly overlapping substrate specificities…
and drugs. However, these enzymes have significantly overlapping substrate specificities…
Multiple substrate binding by cytochrome P450 3A4: estimation of the number of bound substrate molecules
Y Kapelyukh, MJI Paine, JD Maréchal… - Drug metabolism and …, 2008 - ASPET
Cytochrome P450 3A4, a major drug-metabolizing enzyme in man, is well known to show
non-Michaelis-Menten steady-state kinetics for a number of substrates, indicating that more …
non-Michaelis-Menten steady-state kinetics for a number of substrates, indicating that more …
Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines
N Scheer, Y Kapelyukh, L Chatham, A Rode… - Molecular …, 2012 - ASPET
Compared with rodents and many other animal species, the human cytochrome P450 (P450)
Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the …
Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the …
An extensively humanized mouse model to predict pathways of drug disposition and drug/drug interactions, and to facilitate design of clinical trials
CJ Henderson, Y Kapelyukh, N Scheer, A Rode… - Drug metabolism and …, 2019 - ASPET
Species differences in drug metabolism and disposition can confound the extrapolation of in
vivo PK data to man and also profoundly compromise drug efficacy studies owing to …
vivo PK data to man and also profoundly compromise drug efficacy studies owing to …
Modeling human cytochrome P450 2D6 metabolism and drug-drug interaction by a novel panel of knockout and humanized mouse lines
N Scheer, Y Kapelyukh, J McEwan, V Beuger… - Molecular …, 2012 - ASPET
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 …
of up to 25% of all marketed drugs and accounts for significant individual differences in …
In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice
N Scheer, J Ross, Y Kapelyukh, A Rode… - Drug metabolism and …, 2010 - ASPET
Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant
glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a …
glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a …
Defining human pathways of drug metabolism in vivo through the development of a multiple humanized mouse model
N Scheer, Y Kapelyukh, A Rode, S Oswald… - Drug Metabolism and …, 2015 - ASPET
Variability in drug pharmacokinetics is a major factor in defining drug efficacy and side
effects. There remains an urgent need, particularly with the growing use of polypharmacy, to …
effects. There remains an urgent need, particularly with the growing use of polypharmacy, to …
[HTML][HTML] Quantifying ERK activity in response to inhibition of the BRAFV600E-MEK-ERK cascade using mathematical modelling
SJ Hamis, Y Kapelyukh, A McLaren… - British Journal of …, 2021 - nature.com
Background Simultaneous inhibition of multiple components of the BRAF-MEK-ERK cascade
(vertical inhibition) has become a standard of care for treating BRAF-mutant melanoma. …
(vertical inhibition) has become a standard of care for treating BRAF-mutant melanoma. …
A role for cytochrome b5 in the in vivo disposition of anticancer and cytochrome P450 probe drugs in mice
…, RD Finn, S Ronseaux, Y Kapelyukh… - Drug Metabolism and …, 2014 - ASPET
The role of microsomal cytochrome b 5 (Cyb5) in defining the rate of drug metabolism and
disposition has been intensely debated for several decades. Recently we described mouse …
disposition has been intensely debated for several decades. Recently we described mouse …