6b30

From Proteopedia

(Difference between revisions)

Revision as of 21:35, 28 October 2020

Structure of RORgt in complex with a novel inverse agonist 1

Structural highlights

6b30 is a 2 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

A series of novel phenylglycinamides as retinoic acid receptor-related orphan receptor-gamma t (RORgammat) inverse agonists were discovered through optimization of a high-throughput screen hit 1. (R)-N-(2-((3,5-Difluoro-4-(trimethylsilyl)phenyl) amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methylisoxazole-5-carboxamide (22) was identified as one of the best of these compounds. It displayed higher subtype selectivity and specificity over other nuclear receptors and demonstrated in vivo potency to suppress the transcriptional activity of RORgammat in a mouse PD (pharmacodynamic) model upon oral administration.

Discovery of orally efficacious RORgammat inverse agonists, part 1: Identification of novel phenylglycinamides as lead scaffolds.,Shirai J, Tomata Y, Kono M, Ochida A, Fukase Y, Sato A, Masada S, Kawamoto T, Yonemori K, Koyama R, Nakagawa H, Nakayama M, Uga K, Shibata A, Koga K, Okui T, Shirasaki M, Skene R, Sang B, Hoffman I, Lane W, Fujitani Y, Yamasaki M, Yamamoto S Bioorg Med Chem. 2017 Dec 9. pii: S0968-0896(17)31989-2. doi:, 10.1016/j.bmc.2017.12.006. PMID:29262987^[1]

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

References

↑ Shirai J, Tomata Y, Kono M, Ochida A, Fukase Y, Sato A, Masada S, Kawamoto T, Yonemori K, Koyama R, Nakagawa H, Nakayama M, Uga K, Shibata A, Koga K, Okui T, Shirasaki M, Skene R, Sang B, Hoffman I, Lane W, Fujitani Y, Yamasaki M, Yamamoto S. Discovery of orally efficacious RORgammat inverse agonists, part 1: Identification of novel phenylglycinamides as lead scaffolds. Bioorg Med Chem. 2017 Dec 9. pii: S0968-0896(17)31989-2. doi:, 10.1016/j.bmc.2017.12.006. PMID:29262987 doi:http://dx.doi.org/10.1016/j.bmc.2017.12.006

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/6b30"

@@ Line 1: / Line 1: @@
 ==Structure of RORgt in complex with a novel inverse agonist 1==
-<StructureSection load='6b30' size='340' side='right' caption='[[6b30]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
+<StructureSection load='6b30' size='340' side='right'caption='[[6b30]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6b30]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B30 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B30 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6b30]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B30 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6B30 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CFG:N-[(1R)-1-(4-methoxyphenyl)-2-oxo-2-{[4-(trimethylsilyl)phenyl]amino}ethyl]-N-methyl-3-oxo-2,3-dihydro-1,2-oxazole-5-carboxamide'>CFG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CFG:N-[(1R)-1-(4-methoxyphenyl)-2-oxo-2-{[4-(trimethylsilyl)phenyl]amino}ethyl]-N-methyl-3-oxo-2,3-dihydro-1,2-oxazole-5-carboxamide'>CFG</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=6b30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b30 OCA], [http://pdbe.org/6b30 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b30 RCSB], [http://www.ebi.ac.uk/pdbsum/6b30 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b30 ProSAT]</span></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=6b30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b30 OCA], [http://pdbe.org/6b30 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b30 RCSB], [http://www.ebi.ac.uk/pdbsum/6b30 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b30 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Hoffman, I]]
 [[Category: Skene, R J]]

6b30

From Proteopedia

Revision as of 21:35, 28 October 2020

Structure of RORgt in complex with a novel inverse agonist 1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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