Target Information

Target General Infomation
Target ID
T52297
Former ID
TTDR00420
Target Name
Oxysterols receptor LXR-alpha
Gene Name
NR1H3
Synonyms
LXRalpha; Liver X receptor alpha; Nuclear orphan receptor LXR-alpha; Nuclear receptor LXRalpha; NR1H3
Target Type
Research
Disease Atherosclerosis [ICD9: 414.0, 440; ICD10: I70]
Function
Nuclear receptor. Interaction with RXR shifts RXRfrom its role as a silent DNA-binding partner to an active ligand- binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half- sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake throughMYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity).
BioChemical Class
Nuclear hormone receptor
Target Validation
T52297
UniProt ID
Q13133
Sequence
MSLWLGAPVPDIPPDSAVELWKPGAQDASSQAQGGSSCILREEARMPHSAGGTAGVGLEA
AEPTALLTRAEPPSEPTEIRPQKRKKGPAPKMLGNELCSVCGDKASGFHYNVLSCEGCKG
FFRRSVIKGAHYICHSGGHCPMDTYMRRKCQECRLRKCRQAGMREECVLSEEQIRLKKLK
RQEEEQAHATSLPPRASSPPQILPQLSPEQLGMIEKLVAAQQQCNRRSFSDRLRVTPWPM
APDPHSREARQQRFAHFTELAIVSVQEIVDFAKQLPGFLQLSREDQIALLKTSAIEVMLL
ETSRRYNPGSESITFLKDFSYNREDFAKAGLQVEFINPIFEFSRAMNELQLNDAEFALLI
AISIFSADRPNVQDQLQVERLQHTYVEALHAYVSIHHPHDRLMFPRMLMKLVSLRTLSSV
HSEQVFALRLQDKKLPPLLSEIWDVHE
Inhibitor 12,17-dehydroxyriccardin C Drug Info [529375]
12-dehydroxyriccardin C Drug Info [529375]
17-dehydroxyriccardin C Drug Info [529375]
2-(2-hexylphenyl)isoindoline-1,3-dione Drug Info [529375]
2-(2-phenethylphenyl)isoindoline-1,3-dione Drug Info [530220]
2-Benzyl-3-phenyl-7-(trifluoromethyl)-2H-indazole Drug Info [529781]
2-benzyl-4,5,6,7-tetrachloroisoindoline-1,3-dione Drug Info [528834]
4,12,17-dehydroxyriccardin C Drug Info [529375]
4,17-dehydroxyriccardin C Drug Info [529375]
4-dehydroxyriccardin C Drug Info [529375]
5-chloro-2-(4-phenylbutyl)isoindoline-1,3-dione Drug Info [528834]
GSK-9772 Drug Info [529702]
Guttiferone I Drug Info [527525]
GW-3965 Drug Info [529781]
N-{4-[2-(3-Hydroxyphenyl)ethyl]phenyl}phthalimide Drug Info [530220]
N-{4-[2-(3-Methoxyphenyl)ethyl]phenyl}phthalimide Drug Info [530220]
N-{4-[2-(4-Hydroxyphenyl)ethyl]phenyl}phthalimide Drug Info [530220]
N-{4-[2-(4-Methoxyphenyl)ethyl]phenyl}phthalimide Drug Info [530220]
Riccardin C Drug Info [529375]
WAY-214950 Drug Info [529781]
WAY-252623 Drug Info [529781]
WAY-254011 Drug Info [530094]
Agonist 22R-hydroxycholesterol Drug Info [534255]
24(S), 25-epoxycholesterol Drug Info [532179]
24(S)-hydroxycholesterol Drug Info [534311]
27-hydroxycholesterol Drug Info [526122]
acetyl-podocarpic dimer Drug Info [526248]
AZ12260493 Drug Info [543894]
desmosterol Drug Info [528328]
L-783483 Drug Info [535486]
paxilline Drug Info [526684]
Antagonist GSK2033 Drug Info [530809]
SR9238 Drug Info [532155]
Pathways
KEGG Pathway PPAR signaling pathway
Non-alcoholic fatty liver disease (NAFLD)
Hepatitis C
Pathway Interaction Database RXR and RAR heterodimerization with other nuclear receptor
WikiPathways Nuclear Receptors in Lipid Metabolism and Toxicity
Nuclear Receptors Meta-Pathway
PPAR Alpha Pathway
Liver X Receptor Pathway
Adipogenesis
SREBF and miR33 in cholesterol and lipid homeostasis
Nuclear Receptors
References
Ref 52612227-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem. 2001 Oct 19;276(42):38378-87. Epub 2001 Aug 14.
Ref 526248A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCA1 mRNA and stimulating cholesterol efflux. J Biol Chem. 2002 Mar 22;277(12):10021-7. Epub 2002 Jan 14.
Ref 526684A natural product ligand of the oxysterol receptor, liver X receptor. J Pharmacol Exp Ther. 2003 Oct;307(1):291-6. Epub 2003 Jul 31.
Ref 527525J Nat Prod. 2005 Apr;68(4):617-9.Guttiferone I, a new prenylated benzophenone from Garcinia humilis as a liver X receptor ligand.
Ref 528328Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands. J Biol Chem. 2006 Sep 22;281(38):27816-26. Epub 2006 Jul 20.
Ref 528834Bioorg Med Chem Lett. 2007 Jul 15;17(14):3957-61. Epub 2007 Apr 30.Liver X receptor antagonists with a phthalimide skeleton derived from thalidomide-related glucosidase inhibitors.
Ref 529375Bioorg Med Chem. 2008 Apr 15;16(8):4272-85. Epub 2008 Feb 29.Co-existence of alpha-glucosidase-inhibitory and liver X receptor-regulatory activities and their separation by structural development.
Ref 529702J Med Chem. 2008 Sep 25;51(18):5758-65.Structure-guided design of N-phenyl tertiary amines as transrepression-selective liver X receptor modulators with anti-inflammatory activity.
Ref 529781J Med Chem. 2008 Nov 27;51(22):7161-8.Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic triglyceride synthesis.
Ref 530094Bioorg Med Chem. 2009 May 15;17(10):3519-27. Epub 2009 Apr 12.Discovery and SAR of cinnolines/quinolines as liver X receptor (LXR) agonists with binding selectivity for LXRbeta.
Ref 530220Bioorg Med Chem. 2009 Jul 15;17(14):5001-14. Epub 2009 Jun 2.Separation of alpha-glucosidase-inhibitory and liver X receptor-antagonistic activities of phenethylphenyl phthalimide analogs and generation of LXRalpha-selective antagonists.
Ref 530809Discovery of tertiary sulfonamides as potent liver X receptor antagonists. J Med Chem. 2010 Apr 22;53(8):3412-6.
Ref 532155A liver-selective LXR inverse agonist that suppresses hepatic steatosis. ACS Chem Biol. 2013 Mar 15;8(3):559-67.
Ref 532179Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis. Nat Chem Biol. 2013 Feb;9(2):126-33.
Ref 534255An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 1996 Oct 24;383(6602):728-31.
Ref 534311Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem. 1997 Feb 7;272(6):3137-40.
Ref 535486A novel liver X receptor agonist establishes species differences in the regulation of cholesterol 7alpha-hydroxylase (CYP7a). Endocrinology. 2002 Jul;143(7):2548-58.
Ref 543894(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 602).
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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