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5uey

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Revision as of 12:34, 23 September 2020

BRD4_BD2_A-1412838

Structural highlights

5uey 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:
Related:	5uf0, 5uez, 5uex, 5uev, 5uep, 5uet, 5ues, 5uer, 5ueq, 5ueu, 5ueo, 5uew
Gene:	BRD4, HUNK1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.^[1] ^[2]

Function

[BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).

Publication Abstract from PubMed

Members of the BET family of bromodomain containing proteins have been identified as potential targets for blocking proliferation in a variety of cancer cell lines. A two-dimensional NMR fragment screen for binders to the bromodomains of BRD4 identified a phenylpyridazinone fragment with a weak binding affinity (1, Ki = 160 muM). SAR investigation of fragment 1, aided by X-ray structure-based design, enabled the synthesis of potent pyridone and macrocyclic pyridone inhibitors exhibiting single digit nanomolar potency in both biochemical and cell based assays. Advanced analogs in these series exhibited high oral exposures in rodent PK studies and demonstrated significant tumor growth inhibition efficacy in mouse flank xenograft models.

Fragment-Based, Structure-Enabled Discovery of Novel Pyridones and Pyridone Macrocycles as Potent Bromodomain and Extra-Terminal Domain (BET) Family Bromodomain Inhibitors.,Wang L, Pratt JK, Soltwedel T, Sheppard GS, Fidanze SD, Liu D, Hasvold LA, Mantei RA, Holms JH, McClellan WJ, Wendt MD, Wada C, Frey R, Hansen TM, Hubbard R, Park CH, Li L, Magoc TJ, Albert DH, Lin X, Warder SE, Kovar P, Huang X, Wilcox D, Wang R, Rajaraman G, Petros AM, Hutchins CW, Panchal SC, Sun C, Elmore SW, Shen Y, Kati WM, McDaniel KF J Med Chem. 2017 Apr 21. doi: 10.1021/acs.jmedchem.7b00017. PMID:28368119^[3]

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

References

↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
↑ Wang L, Pratt JK, Soltwedel T, Sheppard GS, Fidanze SD, Liu D, Hasvold LA, Mantei RA, Holms JH, McClellan WJ, Wendt MD, Wada C, Frey R, Hansen TM, Hubbard R, Park CH, Li L, Magoc TJ, Albert DH, Lin X, Warder SE, Kovar P, Huang X, Wilcox D, Wang R, Rajaraman G, Petros AM, Hutchins CW, Panchal SC, Sun C, Elmore SW, Shen Y, Kati WM, McDaniel KF. Fragment-Based, Structure-Enabled Discovery of Novel Pyridones and Pyridone Macrocycles as Potent Bromodomain and Extra-Terminal Domain (BET) Family Bromodomain Inhibitors. J Med Chem. 2017 Apr 21. doi: 10.1021/acs.jmedchem.7b00017. PMID:28368119 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b00017

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5uey"

Categories: Human | Large Structures | Park, C H | Signaling protein-inhibitor complex

@@ Line 1: / Line 1: @@
 ==BRD4_BD2_A-1412838==
-<StructureSection load='5uey' size='340' side='right' caption='[[5uey]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
+<StructureSection load='5uey' size='340' side='right'caption='[[5uey]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5uey]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UEY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5uey]] 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=5UEY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UEY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=88M:5-[2-(2,4-DIFLUOROPHENOXY)-5-{[ETHYL(DIHYDROXY)-LAMBDA~4~-SULFANYL]AMINO}PHENYL]-4-ETHOXY-1-METHYLPYRIDIN-2(1H)-ONE'>88M</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=88M:5-[2-(2,4-DIFLUOROPHENOXY)-5-{[ETHYL(DIHYDROXY)-LAMBDA~4~-SULFANYL]AMINO}PHENYL]-4-ETHOXY-1-METHYLPYRIDIN-2(1H)-ONE'>88M</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uf0|5uf0]], [[5uez|5uez]], [[5uex|5uex]], [[5uev|5uev]], [[5uep|5uep]], [[5uet|5uet]], [[5ues|5ues]], [[5uer|5uer]], [[5ueq|5ueq]], [[5ueu|5ueu]], [[5ueo|5ueo]], [[5uew|5uew]]</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=5uey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uey OCA], [http://pdbe.org/5uey PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uey RCSB], [http://www.ebi.ac.uk/pdbsum/5uey PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uey ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([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=5uey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uey OCA], [http://pdbe.org/5uey PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uey RCSB], [http://www.ebi.ac.uk/pdbsum/5uey PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uey ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 </div>
 <div class="pdbe-citations 5uey" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Park, C H]]
 [[Category: Signaling protein-inhibitor complex]]

5uey

From Proteopedia

Revision as of 12:34, 23 September 2020

BRD4_BD2_A-1412838

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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