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PDBsum entry 3fli
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Transcription
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PDB id
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3fli
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Transcription
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Title:
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Discovery of xl335, a highly potent, selective and orally-active agonist of the farnesoid x receptor (fxr)
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Structure:
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Bile acid receptor. Chain: a. Fragment: ligand binding domain. Synonym: farnesoid x-activated receptor, farnesol receptor hrr-1, nuclear receptor subfamily 1 group h member 4, retinoid x receptor- interacting protein 14, rxr-interacting protein 14. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: bar, fxr, hrr1, nr1h4, rip14. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.00Å
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R-factor:
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0.193
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R-free:
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0.243
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Authors:
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P.G.Foster,T.J.Stout
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Key ref:
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B.Flatt
et al.
(2009).
Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR).
J Med Chem,
52,
904-907.
PubMed id:
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Date:
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18-Dec-08
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Release date:
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22-Dec-09
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PROCHECK
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Headers
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References
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Q96RI1
(NR1H4_HUMAN) -
Bile acid receptor from Homo sapiens
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Seq:
Struc:
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486 a.a.
221 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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J Med Chem
52:904-907
(2009)
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PubMed id:
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Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR).
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B.Flatt,
R.Martin,
T.L.Wang,
P.Mahaney,
B.Murphy,
X.H.Gu,
P.Foster,
J.Li,
P.Pircher,
M.Petrowski,
I.Schulman,
S.Westin,
J.Wrobel,
G.Yan,
E.Bischoff,
C.Daige,
R.Mohan.
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ABSTRACT
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Azepino[4,5-b]indoles have been identified as potent agonists of the farnesoid X
receptor (FXR). In vitro and in vivo optimization has led to the discovery of 6m
(XL335, WAY-362450) as a potent, selective, and orally bioavailable FXR agonist
(EC(50) = 4 nM, Eff = 149%). Oral administration of 6m to LDLR(-/-) mice results
in lowering of cholesterol and triglycerides. Chronic administration in an
atherosclerosis model results in significant reduction in aortic arch lesions.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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S.G.Stewart,
E.L.Ghisalberti,
B.W.Skelton,
and
C.H.Heath
(2010).
Formation and reactions of azepino[4,5-b]indoles: an unprecedented ozone reaction in the formation of novel benzo[c]naphthyridinones.
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Org Biomol Chem,
8,
3563-3570.
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Y.Zhang,
L.Yin,
J.Anderson,
H.Ma,
F.J.Gonzalez,
T.M.Willson,
and
P.A.Edwards
(2010).
Identification of novel pathways that control farnesoid X receptor-mediated hypocholesterolemia.
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J Biol Chem,
285,
3035-3043.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
