5f1h: Difference between revisions
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==Crystal structure of the BRD9 bromodamian in complex with BI-9564.== | |||
<StructureSection load='5f1h' size='340' side='right'caption='[[5f1h]], [[Resolution|resolution]] 1.82Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5f1h]] 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=5F1H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F1H 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]] 1.82Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5U6:4-[4-[(DIMETHYLAMINO)METHYL]-2,5-DIMETHOXY-PHENYL]-2-METHYL-2,7-NAPHTHYRIDIN-1-ONE'>5U6</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=5f1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f1h OCA], [https://pdbe.org/5f1h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f1h RCSB], [https://www.ebi.ac.uk/pdbsum/5f1h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f1h ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BRD9_HUMAN BRD9_HUMAN] May play a role in chromatin remodeling and regulation of transcription. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Components of the chromatin remodelling SWI/SNF complex are recurrently mutated in tumours, suggesting that altering the activity of the complex plays a role in oncogenesis. However, the role that the individual subunits play in this process is not clear. We set out to develop an inhibitor compound targeting the bromodomain of BRD9 in order to evaluate its function within the SWI/SNF complex. Here, we present the discovery and development of a potent and selective BRD9 bromodomain inhibitor series based on a new pyridinone-like scaffold. Crystallographic information of the inhibitors bound to BRD9 guided their development with respect to potency for BRD9 and selectivity against BRD4. These compounds modulate BRD9 bromodomain cellular function and display anti-tumour activity in an AML xenograft model. Two chemical probes, BI-7273 (1) and BI-9564 (2), were identified that should prove useful in further exploring BRD9 bromodomain biology in both in vitro and in vivo settings. | |||
Structure-based design of an in vivo active selective BRD9 inhibitor.,Martin LJ, Koegl M, Bader G, Cockcroft XL, Fedorov O, Fiegen D, Gerstberger T, Hofmann MH, Hohmann AF, Kessler D, Knapp S, Knesl P, Kornigg S, Muller S, Nar H, Rogers C, Rumpel K, Schaaf O, Steurer S, Tallant C, Vakoc CR, Zeeb M, Zoephel A, Pearson M, Boehmelt G, McConnell D J Med Chem. 2016 Feb 25. PMID:26914985<ref>PMID:26914985</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5f1h" style="background-color:#fffaf0;"></div> | ||
[[Category: Bader | |||
[[Category: | ==See Also== | ||
[[Category: Weiss-Puxbaum | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bader G]] | |||
[[Category: Martin LJ]] | |||
[[Category: Steurer S]] | |||
[[Category: Weiss-Puxbaum A]] | |||
[[Category: Zoephel A]] | |||
Latest revision as of 11:40, 12 July 2023
Crystal structure of the BRD9 bromodamian in complex with BI-9564.Crystal structure of the BRD9 bromodamian in complex with BI-9564.
Structural highlights
FunctionBRD9_HUMAN May play a role in chromatin remodeling and regulation of transcription. Publication Abstract from PubMedComponents of the chromatin remodelling SWI/SNF complex are recurrently mutated in tumours, suggesting that altering the activity of the complex plays a role in oncogenesis. However, the role that the individual subunits play in this process is not clear. We set out to develop an inhibitor compound targeting the bromodomain of BRD9 in order to evaluate its function within the SWI/SNF complex. Here, we present the discovery and development of a potent and selective BRD9 bromodomain inhibitor series based on a new pyridinone-like scaffold. Crystallographic information of the inhibitors bound to BRD9 guided their development with respect to potency for BRD9 and selectivity against BRD4. These compounds modulate BRD9 bromodomain cellular function and display anti-tumour activity in an AML xenograft model. Two chemical probes, BI-7273 (1) and BI-9564 (2), were identified that should prove useful in further exploring BRD9 bromodomain biology in both in vitro and in vivo settings. Structure-based design of an in vivo active selective BRD9 inhibitor.,Martin LJ, Koegl M, Bader G, Cockcroft XL, Fedorov O, Fiegen D, Gerstberger T, Hofmann MH, Hohmann AF, Kessler D, Knapp S, Knesl P, Kornigg S, Muller S, Nar H, Rogers C, Rumpel K, Schaaf O, Steurer S, Tallant C, Vakoc CR, Zeeb M, Zoephel A, Pearson M, Boehmelt G, McConnell D J Med Chem. 2016 Feb 25. PMID:26914985[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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