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4zjr

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Revision as of 14:22, 29 March 2017

RORgamma in complex with inverse agonist 48

Structural highlights

4zjr is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

Publication Abstract from PubMed

RORgammat is a pivotal regulator of a pro-inflammatory gene expression program implicated in the pathology of several major human immune-mediated diseases. Evidence from mouse models demonstrates that genetic or pharmacological inhibition of RORgamma activity can block the production of pathogenic cytokines, including IL-17, and convey therapeutic benefit. We have identified and developed a biaryl-carboxylamide series of RORgamma inverse agonists via a structure based design approach. Co-crystal structures of compounds 16 and 48 supported the design approach and confirmed the key interactions with RORgamma protein; the hydrogen bonding with His479 was key to the significant improvement in inverse agonist effect. The results have shown this is a class of potent and selective RORgamma inverse agonists, with demonstrated oral bioavailability in rodents.

Discovery of biaryl carboxylamides as potent RORgamma inverse agonists.,Chao J, Enyedy I, Van Vloten K, Marcotte D, Guertin K, Hutchings R, Powell N, Jones H, Bohnert T, Peng CC, Silvian L, Hong VS, Little K, Banerjee D, Peng L, Taveras A, Viney JL, Fontenot J Bioorg Med Chem Lett. 2015 Aug 1;25(15):2991-7. doi: 10.1016/j.bmcl.2015.05.026. , Epub 2015 May 23. PMID:26048806^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chao J, Enyedy I, Van Vloten K, Marcotte D, Guertin K, Hutchings R, Powell N, Jones H, Bohnert T, Peng CC, Silvian L, Hong VS, Little K, Banerjee D, Peng L, Taveras A, Viney JL, Fontenot J. Discovery of biaryl carboxylamides as potent RORgamma inverse agonists. Bioorg Med Chem Lett. 2015 Aug 1;25(15):2991-7. doi: 10.1016/j.bmcl.2015.05.026. , Epub 2015 May 23. PMID:26048806 doi:http://dx.doi.org/10.1016/j.bmcl.2015.05.026

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4zjr"

Categories: Marcotte, D J | Inverse agonist | Rorgamma ligand binding domain | Transcription

@@ Line 1: / Line 1: @@
 ==RORgamma in complex with inverse agonist 48==
 <StructureSection load='4zjr' size='340' side='right' caption='[[4zjr]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4zjr]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZJR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZJR FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4P3:6-CHLORO-4-[(2-CHLORO-6-FLUOROBENZOYL)(METHYL)AMINO]-3-(2,2,2-TRIFLUOROETHOXY)BIPHENYL-3-CARBOXAMIDE'>4P3</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=4zjr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zjr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zjr RCSB], [http://www.ebi.ac.uk/pdbsum/4zjr PDBsum]</span></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=4zjr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zjr OCA], [http://pdbe.org/4zjr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zjr RCSB], [http://www.ebi.ac.uk/pdbsum/4zjr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zjr ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4zjr" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4zjr

From Proteopedia

Revision as of 14:22, 29 March 2017

RORgamma in complex with inverse agonist 48

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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