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Flo Ramirez and Harry Tabata
Authors
● N. Scheer, A. Rode, B. Zevnik, and S.
Niehaves receive income from
TaconicArtemis
(You design the study, we'll design the mouse.)
● J. Ross and C.R. Wolf receive income from
CXR Biosciences (toxicology and pharmcokinetics)
● N. Faust receives income from Amaxa AG
(Gene Transfer technology)
Background
● PXR
o
Pregnane X receptor
● CAR
o
Constitutive androstane receptor
● Phase 1, 2 , 3
o
Detoxifying mechanism for xenobiotics
● Created mice with human PXR and CAR
CAR and PXR Crosstalk
NR1I Nuclear Receptor
family
PXR Analysis
CAR analysis
In Vitro vs In Vivo
● Studies of in vitro showed that both PXR and
CAR played a significant role of induction of
Cyp3a11 and Cyp2b10 by PB.
● In vivo studies showed that CAR had a more
significant role
Big Picture and Implications
● Mice models with human genes
● Drug safety and efficacy in humans
● Possible application in drug development
Critiques
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Results a tad unclear
inconsistent use of abbreviations
Data not shown listed at least 12 times
Did not show or reference data to actual
human studies