5kyj
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==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]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5kyj]] is a 4 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KYJ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5i4v|5i4v]], [[5kya|5kya]]</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=5kyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kyj OCA], [http://pdbe.org/5kyj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kyj RCSB], [http://www.ebi.ac.uk/pdbsum/5kyj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kyj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[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). [[http://www.uniprot.org/uniprot/RXRB_HUMAN RXRB_HUMAN]] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Specifically binds 9-cis retinoic acid (9C-RA). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5kyj" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Chen, G]] | ||
| + | [[Category: McKeever, B M]] | ||
| + | [[Category: Chemical modulator]] | ||
| + | [[Category: Dna binding protein]] | ||
| + | [[Category: Liver x receptor]] | ||
| + | [[Category: Lxrbeta-lbd/rxrbeta-lbd heterodimer]] | ||
| + | [[Category: Nuclear receptor]] | ||
| + | [[Category: Retinoic acid x receptor]] | ||
Revision as of 13:57, 21 September 2016
Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core
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