6q2w

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human ROR gamma LBD in complex with a quinoline sulfonamide inverse agonist

Structural highlights

6q2w is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.99Å
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

A high-throughput screen against Inventiva's compound library using a Gal4/RORgamma-LBD luciferase reporter gene assay led to the discovery of a new series of quinoline sulphonamides as RORgamma inhibitors, eventually giving rise to a lead compound having an interesting in vivo profile after oral administration. This lead was evaluated in a target engagement model in mouse, where it reduced IL-17 cytokine production after immune challenge. It also proved to be active in a multiple sclerosis model (EAE) where it reduced the disease score. The synthesis, structure activity relationship (SAR) and biological activity of these derivatives is described herein.

Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active RORgamma inverse agonists.,Amaudrut J, Argiriadi MA, Barth M, Breinlinger EC, Bressac D, Broqua P, Calderwood DJ, Chatar M, Cusack KP, Gauld SB, Jacquet S, Kamath RV, Kort ME, Lepais V, Luccarini JM, Masson P, Montalbetti C, Mounier L, Potin D, Poupardin O, Rouaud S, Spitzer L, Wallace CD Bioorg Med Chem Lett. 2019 May 9. pii: S0960-894X(19)30301-4. doi:, 10.1016/j.bmcl.2019.05.015. PMID:31101472^[1]

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

References

↑ Amaudrut J, Argiriadi MA, Barth M, Breinlinger EC, Bressac D, Broqua P, Calderwood DJ, Chatar M, Cusack KP, Gauld SB, Jacquet S, Kamath RV, Kort ME, Lepais V, Luccarini JM, Masson P, Montalbetti C, Mounier L, Potin D, Poupardin O, Rouaud S, Spitzer L, Wallace CD. Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active RORgamma inverse agonists. Bioorg Med Chem Lett. 2019 May 9. pii: S0960-894X(19)30301-4. doi:, 10.1016/j.bmcl.2019.05.015. PMID:31101472 doi:http://dx.doi.org/10.1016/j.bmcl.2019.05.015

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/6q2w"

@@ Line 3: / Line 3: @@
 <StructureSection load='6q2w' size='340' side='right'caption='[[6q2w]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6q2w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q2W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q2W FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6q2w]] is a 2 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=6Q2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q2W FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HBW:(2~{S})-1-[2,4-bis(chloranyl)-3-[[4-imidazol-1-yl-2-(trifluoromethyl)quinolin-8-yl]oxymethyl]phenyl]sulfonyl-~{N}-methyl-pyrrolidine-2-carboxamide'>HBW</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.99&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RORC, NR1F3, RORG, RZRG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HBW:(2~{S})-1-[2,4-bis(chloranyl)-3-[[4-imidazol-1-yl-2-(trifluoromethyl)quinolin-8-yl]oxymethyl]phenyl]sulfonyl-~{N}-methyl-pyrrolidine-2-carboxamide'>HBW</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=6q2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q2w OCA], [http://pdbe.org/6q2w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q2w RCSB], [http://www.ebi.ac.uk/pdbsum/6q2w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q2w ProSAT]</span></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=6q2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q2w OCA], [https://pdbe.org/6q2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q2w RCSB], [https://www.ebi.ac.uk/pdbsum/6q2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q2w ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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.
+[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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Amaudrut, J]]
+[[Category: Amaudrut J]]
-[[Category: Argiriadi, M A]]
+[[Category: Argiriadi MA]]
-[[Category: Barth, M]]
+[[Category: Barth M]]
-[[Category: Breinlinger, E C]]
+[[Category: Breinlinger EC]]
-[[Category: Calderwood, D J]]
+[[Category: Calderwood DJ]]
-[[Category: Ciesielski, F]]
+[[Category: Ciesielski F]]
-[[Category: Cusack, K P]]
+[[Category: Cusack KP]]
-[[Category: Kort, M E]]
+[[Category: Kort ME]]
-[[Category: Montalbetti, C]]
+[[Category: Montalbetti C]]
-[[Category: Potin, D]]
+[[Category: Potin D]]
-[[Category: Poupardin, O]]
+[[Category: Poupardin O]]
-[[Category: Spitzer, L]]
+[[Category: Spitzer L]]
-[[Category: Inverse agonist]]
-[[Category: Nuclear hormone receptor]]
-[[Category: Ror gamma]]
-[[Category: Transcription]]

6q2w

From Proteopedia

Current revision

Crystal structure of human ROR gamma LBD in complex with a quinoline sulfonamide inverse agonist

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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