View source for 6vqf


==CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C (NHIS-RORGT(244- 487)-L6-SRC1(678-692)) IN COMPLEX WITH AN INVERSE AGONIST==
<StructureSection load='6vqf' size='340' side='right'caption='[[6vqf]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vqf]] is a 1 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=6VQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VQF 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=R7V:(1R,3S,4R)-4-[(3aR,9bR)-9b-[(4-fluorophenyl)sulfonyl]-7-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-1,2,3a,4,5,9b-hexahydro-3H-benzo[e]indole-3-carbonyl]-3-methylcyclohexane-1-carboxylic+acid'>R7V</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=6vqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vqf OCA], [https://pdbe.org/6vqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vqf RCSB], [https://www.ebi.ac.uk/pdbsum/6vqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vqf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock.
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== Publication Abstract from PubMed ==
Novel tricyclic analogues were designed, synthesized, and evaluated as RORgammat inverse agonists. Several of these compounds were potent in an IL-17 human whole blood assay and exhibited excellent oral bioavailability in mouse pharmacokinetic studies. This led to the identification of compound 5, which displayed dose-dependent inhibition of IL-17F production in a mouse IL-2/IL-23 stimulated pharmacodynamic model. In addition, compound 5 was studied in mouse acanthosis and imiquimod-induced models of skin inflammation, where it demonstrated robust efficacy comparable to a positive control. As a result of this excellent overall profile, compound 5 (BMS-986251) was selected as a clinically viable developmental candidate.

Discovery of BMS-986251: A Clinically Viable, Potent, and Selective RORgammat Inverse Agonist.,Cherney RJ, Cornelius LAM, Srivastava A, Weigelt CA, Marcoux D, Duan JJ, Shi Q, Batt DG, Liu Q, Yip S, Wu DR, Ruzanov M, Sack J, Khan J, Wang J, Yarde M, Cvijic ME, Mathur A, Li S, Shuster D, Khandelwal P, Borowski V, Xie J, Obermeier M, Fura A, Stefanski K, Cornelius G, Tino JA, Macor JE, Salter-Cid L, Denton R, Zhao Q, Carter PH, Dhar TGM ACS Med Chem Lett. 2020 Mar 31;11(6):1221-1227. doi:, 10.1021/acsmedchemlett.0c00063. eCollection 2020 Jun 11. PMID:32551004<ref>PMID:32551004</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6vqf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sack JS]]