9syi: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

The ~~entry 9syi~~ is ~~ON HOLD until Paper~~ Publication

==Crystal structure of TEAD4 in complex with compound 9==

== Structural highlights ==

<table><tr><td colspan='2'>[[9syi]] 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=9SYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SYI FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.102Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ICN:2-[(2~{S})-5-chloranyl-2-phenyl-2-[(2~{S})-pyrrolidin-2-yl]-3~{H}-1-benzofuran-4-yl]-3-fluoranyl-4-methoxy-benzamide'>A1ICN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=U3O:(2~{R})-2-[2-chloranyl-5-[2-chloranyl-4-(trifluoromethyl)phenoxy]phenyl]sulfanylpropanoic+acid'>U3O</scene></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=9syi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9syi OCA], [https://pdbe.org/9syi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9syi RCSB], [https://www.ebi.ac.uk/pdbsum/9syi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9syi ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/TEAD4_HUMAN TEAD4_HUMAN] Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif.<ref>PMID:18579750</ref> <ref>PMID:19324877</ref>

== Publication Abstract from PubMed ==

The interaction of transcriptional enhanced associate domain (TEAD) and transcriptional coactivator yes-associated protein (YAP) mediates oncogenic functions downstream of the Hippo pathway. In this report, we outline our efforts to find a potent inhibitor of this protein-protein interaction with suitable properties for clinical evaluation. We detail the medicinal chemistry program that led to the discovery of IAG933, an inhibitor with a balanced ADME profile, enabling its evaluation as a potential treatment option in clinical settings.

~~Authors~~:

Discovery of Clinical Candidate IAG933, a Potent YAP-TEAD PPI Disrupter.,Vogtle M, Sellner H, Chapeau E, Furet P, Salem B, Le Douget M, Bordas V, Groell JM, Le Goff AL, Rouzet C, Wietlisbach T, Zimmermann T, McKenna J, Brocklehurst CE, Chene P, Wartmann M, Scheufler C, Kallen J, de Kanter R, Harlfinger S, Zecri F, Schmelzle T, Soldermann N J Med Chem. 2026 Mar 4. doi: 10.1021/acs.jmedchem.5c03009. PMID:41780024<ref>PMID:41780024</ref>

~~Description~~:

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

[[Category: ~~Unreleased~~ Structures]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Izaac A]]

[[Category: Scheufler C]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9syi is ON HOLD  until Paper Publication
+==Crystal structure of TEAD4 in complex with compound 9==
+<StructureSection load='9syi' size='340' side='right'caption='[[9syi]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9syi]] 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=9SYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SYI FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.102&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ICN:2-[(2~{S})-5-chloranyl-2-phenyl-2-[(2~{S})-pyrrolidin-2-yl]-3~{H}-1-benzofuran-4-yl]-3-fluoranyl-4-methoxy-benzamide'>A1ICN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=U3O:(2~{R})-2-[2-chloranyl-5-[2-chloranyl-4-(trifluoromethyl)phenoxy]phenyl]sulfanylpropanoic+acid'>U3O</scene></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=9syi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9syi OCA], [https://pdbe.org/9syi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9syi RCSB], [https://www.ebi.ac.uk/pdbsum/9syi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9syi ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/TEAD4_HUMAN TEAD4_HUMAN] Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif.<ref>PMID:18579750</ref> <ref>PMID:19324877</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The interaction of transcriptional enhanced associate domain (TEAD) and transcriptional coactivator yes-associated protein (YAP) mediates oncogenic functions downstream of the Hippo pathway. In this report, we outline our efforts to find a potent inhibitor of this protein-protein interaction with suitable properties for clinical evaluation. We detail the medicinal chemistry program that led to the discovery of IAG933, an inhibitor with a balanced ADME profile, enabling its evaluation as a potential treatment option in clinical settings.
-Authors:
+Discovery of Clinical Candidate IAG933, a Potent YAP-TEAD PPI Disrupter.,Vogtle M, Sellner H, Chapeau E, Furet P, Salem B, Le Douget M, Bordas V, Groell JM, Le Goff AL, Rouzet C, Wietlisbach T, Zimmermann T, McKenna J, Brocklehurst CE, Chene P, Wartmann M, Scheufler C, Kallen J, de Kanter R, Harlfinger S, Zecri F, Schmelzle T, Soldermann N J Med Chem. 2026 Mar 4. doi: 10.1021/acs.jmedchem.5c03009. PMID:41780024<ref>PMID:41780024</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9syi" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Izaac A]]
+[[Category: Scheufler C]]