7jtm

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C (NHIS-RORGT(244-487)-L6-SRC1(6T78-692) IN COMPLEX WITH A TRICYCLIC SULFONE RORGT INVERSE AGONIST

Structural highlights

7jtm is a 1 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 2.43Å
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

In order to rapidly develop C6 and C8 SAR of our reported tricyclic sulfone series of RORgammat inverse agonists, a late-stage bromination was employed. Although not regioselective, the bromination protocol allowed us to explore new substitution patterns/vectors that otherwise would have to be incorporated at the very beginning of the synthesis. Based on the SAR obtained from this exercise, compound 15 bearing a C8 fluorine was developed as a very potent and selective RORgammat inverse agonist. This analog's in vitro profile, pharmacokinetic (PK) data and efficacy in an IL-23 induced mouse acanthosis model will be discussed.

Tricyclic Sulfones as Potent, Selective and Efficacious RORgammat Inverse Agonists - Exploring C6 and C8 SAR Using Late-Stage Functionalization.,Shi Q, Xiao Z, Yang MG, Marcoux D, Cherney RJ, Yip S, Li P, Wu DR, Weigelt CA, Sack J, Khan J, Ruzanov M, Wang J, Yarde M, Ellen Cvijic M, Li S, Shuster DJ, Xie J, Sherry T, Obermeier M, Fura A, Stefanski K, Cornelius G, Chacko S, Shu YZ, Khandelwal P, Hynes J Jr, Tino JA, Salter-Cid L, Denton R, Zhao Q, Murali Dhar TG Bioorg Med Chem Lett. 2020 Aug 31:127521. doi: 10.1016/j.bmcl.2020.127521. PMID:32882417^[1]

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

References

↑ Shi Q, Xiao Z, Yang MG, Marcoux D, Cherney RJ, Yip S, Li P, Wu DR, Weigelt CA, Sack J, Khan J, Ruzanov M, Wang J, Yarde M, Ellen Cvijic M, Li S, Shuster DJ, Xie J, Sherry T, Obermeier M, Fura A, Stefanski K, Cornelius G, Chacko S, Shu YZ, Khandelwal P, Hynes J Jr, Tino JA, Salter-Cid L, Denton R, Zhao Q, Murali Dhar TG. Tricyclic Sulfones as Potent, Selective and Efficacious RORgammat Inverse Agonists - Exploring C6 and C8 SAR Using Late-Stage Functionalization. Bioorg Med Chem Lett. 2020 Aug 31:127521. doi: 10.1016/j.bmcl.2020.127521. PMID:32882417 doi:http://dx.doi.org/10.1016/j.bmcl.2020.127521

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/7jtm"

Categories: Homo sapiens | Large Structures | Sack JS

@@ Line 3: / Line 3: @@
 <StructureSection load='7jtm' size='340' side='right'caption='[[7jtm]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7jtm]] 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=7JTM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7JTM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7jtm]] 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=7JTM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JTM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VK7:trans-4-[(3aR,9bR)-8-cyano-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]cyclohexane-1-carboxylic+acid'>VK7</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]] 2.43&#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=VK7:trans-4-[(3aR,9bR)-8-cyano-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]cyclohexane-1-carboxylic+acid'>VK7</scene></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=7jtm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jtm OCA], [http://pdbe.org/7jtm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7jtm RCSB], [http://www.ebi.ac.uk/pdbsum/7jtm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7jtm 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=7jtm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jtm OCA], [https://pdbe.org/7jtm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jtm RCSB], [https://www.ebi.ac.uk/pdbsum/7jtm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jtm 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: Sack, J S]]
+[[Category: Sack JS]]
-[[Category: Inve agonist]]
-[[Category: Ligand-binding domain]]
-[[Category: Nuclear hormone receptor]]
-[[Category: Rorgt]]
-[[Category: Transferase]]
-[[Category: Transferase-transferase inhibitor complex]]

7jtm

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C (NHIS-RORGT(244-487)-L6-SRC1(6T78-692) IN COMPLEX WITH A TRICYCLIC SULFONE RORGT INVERSE AGONIST

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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