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Chapter 3.3

ADMS 3502 Chapter 3.3: ADMS 3502 Chapter 3.: Farnesoid X receptor (FXR)


Department
Administrative Studies
Course Code
ADMS 3502
Professor
Cristobal Sanchez- Rodriguez
Chapter
3.3

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Farnesoid X receptor (FXR)
Receptor
Endogenous
ligand
Homo or
hetero?
Physiologic pathway/function
Agonists
Antagonists
Liver X
receptor(LXR)
LXR
LXR
(2 genes)
24,25-
epoxycholesterol,
27-
hydroxycholester
ol
Heterodi
mer
Controls cholesterol intestinal
absorption, cholesterol catabolism,
reverse cholesterol transport from
peripheral tissues to liver for
excretion of bile
-one target of LXR is CYP7A1 which
converts cholesterol to bile acids
-----
- drug are entering
clinical testing:
promotes reverse
cholesterol
transport and
reduces
atherosclerosis in
mice
-----
Farnesoid X
receptor (FXR)
FXR humans
(rodents have
FXR and FXR)
Bile acids
(chenodeoxycholi
c acid)
Heterodi
mer
Regulates bile acid homeostasis
Decreases bile acid secretion into
intestine
Potential therapeutic target for
controlling bile acid diarrhea
-----
Obeticholic acid
(phase II clinical trial
for secondary bile
acid malabsorption
and chronic
diarrhea)
Guggulsterone
(native herbal
indian med; resin
from commiphora
mukul tree)
Pregnane X
receptor(PXR)
5b-pregnane-
3,20-dione
But
PROMISCUOUS
(large binding
pocket)
Heterodi
mer
Regulates phase I and II enzymes
esp CYP3A4 and UGTs (important for
drug metabolism CYP3A4
metabolizes 50% of drugs in market;
so altering it can lead to many DDIs)
Regulates drug transporters P-gp
Rifampicin,
phenobarbital,
nifedipine,
clotrimazole, RU486,
tamoxifen, taxol,
hyperforin (St.
Johns Wort)
Sulforaphane
(cruciferous
vegetable)
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