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PDBsum entry 5avi
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Transcription
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PDB id
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5avi
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PDB id:
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Transcription
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Title:
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Crystal structure of lxralpha in complex with tert-butyl benzoate analog, compound 4
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Structure:
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Oxysterols receptor lxr-alpha. Chain: a, c. Fragment: ligand binding domain, unp residues 182-447. Synonym: liver x receptor alpha,nuclear receptor subfamily 1 group h member 3. Engineered: yes. Nuclear receptor coactivator 1. Chain: b, d. Fragment: unp residues 676-700.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: nr1h3, lxra. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606
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Resolution:
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2.70Å
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R-factor:
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0.247
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R-free:
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0.274
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Authors:
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Y.Matsui,H.Hanzawa,K.Tamaki
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Key ref:
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Y.Matsui
et al.
(2015).
Discovery and structure-guided optimization of tert-butyl 6-(phenoxymethyl)-3-(trifluoromethyl)benzoates as liver X receptor agonists.
Bioorg Med Chem Lett,
25,
3914-3920.
PubMed id:
DOI:
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Date:
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16-Jun-15
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Release date:
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26-Aug-15
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PROCHECK
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Headers
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References
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Enzyme class:
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Chains B, D:
E.C.2.3.1.48
- histone acetyltransferase.
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Reaction:
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L-lysyl-[protein] + acetyl-CoA = N6-acetyl-L-lysyl-[protein] + CoA + H+
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L-lysyl-[protein]
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+
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acetyl-CoA
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=
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N(6)-acetyl-L-lysyl-[protein]
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+
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CoA
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Bioorg Med Chem Lett
25:3914-3920
(2015)
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PubMed id:
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Discovery and structure-guided optimization of tert-butyl 6-(phenoxymethyl)-3-(trifluoromethyl)benzoates as liver X receptor agonists.
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Y.Matsui,
T.Yamaguchi,
T.Yamazaki,
M.Yoshida,
M.Arai,
N.Terasaka,
S.Honzumi,
K.Wakabayashi,
S.Hayashi,
D.Nakai,
H.Hanzawa,
K.Tamaki.
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ABSTRACT
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To obtain potent liver X receptor (LXR) agonists, a structure-activity
relationship study was performed on a series of tert-butyl benzoate analogs. As
the crystal structure analysis suggested applicable interactions between the LXR
ligand-binding domain and the ligands, two key functional groups were
introduced. The introduction of the hydroxyl group on the C6-position of the
benzoate part enhanced the agonistic activity in a cell-based assay, and the
carboxyl group in terminal improved the pharmacokinetic profile in mice,
respectively. The obtained compound 32b increased blood ABCA1 mRNA expression
without plasma TG elevation in both mice and cynomolgus monkeys.
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Links
