View source for 5kyj


==Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core==
<StructureSection load='5kyj' size='340' side='right'caption='[[5kyj]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kyj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KYJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6Y8:(6~{R})-5-(5-FLUORANYL-2-METHOXY-PYRIMIDIN-4-YL)-2-(3-METHYLSULFONYLPHENYL)-6-PROPAN-2-YL-4,6-DIHYDROPYRROLO[3,4-C]PYRAZOLE'>6Y8</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5kyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kyj OCA], [https://pdbe.org/5kyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kyj RCSB], [https://www.ebi.ac.uk/pdbsum/5kyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kyj ProSAT]</span></td></tr>
</table>
== Function ==
[https://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).
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== Publication Abstract from PubMed ==
Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Abeta) and thus to have potential for the treatment of Alzheimer's disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Abeta levels was detected.

Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.,Tice CM, Noto PB, Fan KY, Zhao W, Lotesta SD, Dong C, Marcus AP, Zheng YJ, Chen G, Wu Z, Van Orden R, Zhou J, Bukhtiyarov Y, Zhao Y, Lipinski K, Howard L, Guo J, Kandpal G, Meng S, Hardy A, Krosky P, Gregg RE, Leftheris K, McKeever BM, Singh SB, Lala D, McGeehan GM, Zhuang L, Claremon DA Bioorg Med Chem Lett. 2016 Aug 29. pii: S0960-894X(16)30921-0. doi:, 10.1016/j.bmcl.2016.08.089. PMID:27599745<ref>PMID:27599745</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5kyj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Liver X receptor|Liver X receptor]]
*[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen G]]
[[Category: McKeever BM]]