5jy3

<StructureSection load='5jy3' size='340' side='right' caption='[[5jy3]], [[Resolution|resolution]] 2.40&Aring;' scene=''>

<table><tr><td colspan='2'>[[5jy3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JY3 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6OX:2-[2-[2-[2,6-BIS(CHLORANYL)PHENYL]PROPAN-2-YL]-1-[2-FLUORANYL-4-[3-FLUORANYL-4-(HYDROXYMETHYL)-5-METHYLSULFONYL-PHENYL]PHENYL]IMIDAZOL-4-YL]PROPAN-2-OL'>6OX</scene>, <scene name='pdbligand=BU1:1,4-BUTANEDIOL'>BU1</scene></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5jy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jy3 OCA], [http://pdbe.org/5jy3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jy3 RCSB], [http://www.ebi.ac.uk/pdbsum/5jy3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jy3 ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/NR1H2_HUMAN NR1H2_HUMAN]] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity).

Introducing a uniquely substituted phenyl sulfone into a series of biphenyl imidazole liver X receptor (LXR) agonists afforded a dramatic potency improvement for induction of ATP binding cassette transporters, ABCA1 and ABCG1, in human whole blood. The agonist series demonstrated robust LXRbeta activity (&gt;70%) with low partial LXRalpha agonist activity (&lt;25%) in cell assays, providing a window between desired blood cell ABCG1 gene induction in cynomolgus monkeys and modest elevation of plasma triglycerides for agonist 15. The addition of polarity to the phenyl sulfone also reduced binding to the plasma protein, human alpha-1-acid glycoprotein. Agonist 15 was selected for clinical development based on the favorable combination of in vitro properties, excellent pharmacokinetic parameters, and a favorable lipid profile.

 

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== References ==

[[Category: Muckelbauer, J K]]

[[Category: Lxr-b]]

[[Category: Lxrb]]

[[Category: Unr]]