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5lwp

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Revision as of 10:52, 12 August 2020

Discovery of phenoxyindazoles and phenylthioindazoles as RORg inverse agonists

Structural highlights

5lwp is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	RORC, NR1F3, RORG, RZRG (HUMAN)
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

Targeting the IL17 pathway and more specifically the nuclear receptor RORgamma is thought to be beneficial in multiple skin disorders. The Letter describes the discovery of phenoxyindazoles and thiophenoxy indazoles as potent RORgamma inverse agonists. Optimization of the potency and efforts to mitigate the phototoxic liability of the series are presented. Finally, crystallization of the lead compound revealed that the series bound to an allosteric site of the nuclear receptor. Such compounds could be useful as tool compounds for understanding the impact of topical treatment on skin disease models.

Discovery of phenoxyindazoles and phenylthioindazoles as RORgamma inverse agonists.,Ouvry G, Bouix-Peter C, Ciesielski F, Chantalat L, Christin O, Comino C, Duvert D, Feret C, Harris CS, Lamy L, Luzy AP, Musicki B, Orfila D, Pascau J, Parnet V, Perrin A, Pierre R, Polge G, Raffin C, Rival Y, Taquet N, Thoreau E, Hennequin LF Bioorg Med Chem Lett. 2016 Dec 1;26(23):5802-5808. doi:, 10.1016/j.bmcl.2016.10.023. Epub 2016 Oct 12. PMID:27815118^[1]

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

References

↑ Ouvry G, Bouix-Peter C, Ciesielski F, Chantalat L, Christin O, Comino C, Duvert D, Feret C, Harris CS, Lamy L, Luzy AP, Musicki B, Orfila D, Pascau J, Parnet V, Perrin A, Pierre R, Polge G, Raffin C, Rival Y, Taquet N, Thoreau E, Hennequin LF. Discovery of phenoxyindazoles and phenylthioindazoles as RORgamma inverse agonists. Bioorg Med Chem Lett. 2016 Dec 1;26(23):5802-5808. doi:, 10.1016/j.bmcl.2016.10.023. Epub 2016 Oct 12. PMID:27815118 doi:http://dx.doi.org/10.1016/j.bmcl.2016.10.023

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/5lwp"

@@ Line 1: / Line 1: @@
 ==Discovery of phenoxyindazoles and phenylthioindazoles as RORg inverse agonists==
-<StructureSection load='5lwp' size='340' side='right' caption='[[5lwp]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='5lwp' size='340' side='right'caption='[[5lwp]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5lwp]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LWP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LWP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5lwp]] is a 1 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=5LWP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LWP FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=79U:4-[3-[2-CHLORANYL-6-(TRIFLUOROMETHYL)PHENOXY]-5-(DIMETHYLCARBAMOYL)INDAZOL-1-YL]BENZOIC+ACID'>79U</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=79U:4-[3-[2-CHLORANYL-6-(TRIFLUOROMETHYL)PHENOXY]-5-(DIMETHYLCARBAMOYL)INDAZOL-1-YL]BENZOIC+ACID'>79U</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=5lwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lwp OCA], [http://pdbe.org/5lwp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lwp RCSB], [http://www.ebi.ac.uk/pdbsum/5lwp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lwp ProSAT]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5lwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lwp OCA], [http://pdbe.org/5lwp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lwp RCSB], [http://www.ebi.ac.uk/pdbsum/5lwp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lwp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Bouix-Peter, C]]
 [[Category: Chantalat, L]]

5lwp

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Revision as of 10:52, 12 August 2020

Discovery of phenoxyindazoles and phenylthioindazoles as RORg inverse agonists

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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