6ggn - Revision history

OCA at 07:00, 24 October 2018

OCA — Wed, 24 Oct 2018 07:00:20 GMT

←Older revision		Revision as of 07:00, 24 October 2018
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	<StructureSection load='6ggn' size='340' side='right' caption='[[6ggn]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6ggn' size='340' side='right' caption='[[6ggn]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ggn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GGN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GGN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ggn]] 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=6GGN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GGN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EYH:(4~{S})-4-(4-chloranyl-2-methyl-phenyl)-5-(5-chloranyl-2-methyl-phenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4~{H}-pyrrolo[3,4-d]imidazol-6-one'>EYH</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EYH:(4~{S})-4-(4-chloranyl-2-methyl-phenyl)-5-(5-chloranyl-2-methyl-phenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4~{H}-pyrrolo[3,4-d]imidazol-6-one'>EYH</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MDM2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></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=6ggn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ggn OCA], [http://pdbe.org/6ggn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ggn RCSB], [http://www.ebi.ac.uk/pdbsum/6ggn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ggn ProSAT]</span></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=6ggn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ggn OCA], [http://pdbe.org/6ggn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ggn RCSB], [http://www.ebi.ac.uk/pdbsum/6ggn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ggn ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: RING-type E3 ubiquitin transferase]]		[[Category: RING-type E3 ubiquitin transferase]]
	[[Category: Kallen, J]]		[[Category: Kallen, J]]

OCA at 08:12, 26 September 2018

OCA — Wed, 26 Sep 2018 08:12:54 GMT

←Older revision		Revision as of 08:12, 26 September 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6ggn is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor==
		+	<StructureSection load='6ggn' size='340' side='right' caption='[[6ggn]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ggn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GGN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GGN FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EYH:(4~{S})-4-(4-chloranyl-2-methyl-phenyl)-5-(5-chloranyl-2-methyl-phenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4~{H}-pyrrolo[3,4-d]imidazol-6-one'>EYH</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></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=6ggn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ggn OCA], [http://pdbe.org/6ggn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ggn RCSB], [http://www.ebi.ac.uk/pdbsum/6ggn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ggn ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Small molecule inhibitors of the p53-MDM2 protein complex are under intense investigation in clinical trials as anti-cancer agents, including our first generation inhibitor NVP-CGM097. We recently described the rational design of a novel pyrazolopyrrolidinone core as a new lead structure and now we report on the synthesis and optimization of this to provide a highly potent lead compound. This new compound displayed excellent oral efficacy in our preclinical mechanistic in vivo model and marked a significant milestone towards the identification of our second generation clinical candidate NVP-HDM201.

-	~~Authors: Kallen~~, J.	+	In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor.,Vaupel A, Holzer P, Ferretti S, Guagnano V, Kallen J, Mah R, Masuya K, Ruetz S, Rynn C, Schlapbach A, Stachyra T, Stutz S, Todorov M, Jeay S, Furet P Bioorg Med Chem Lett. 2018 Aug 26. pii: S0960-894X(18)30703-0. doi:, 10.1016/j.bmcl.2018.08.027. PMID:30217415<ref>PMID:30217415</ref>

-	~~Description: In vitro and in vivo characterization of a novel~~, ~~highly potent p53~~-~~MDM2 inhibitor~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6ggn" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: RING-type E3 ubiquitin transferase]]
	[[Category: Kallen, J]]		[[Category: Kallen, J]]
		+	[[Category: Cell cycle]]
		+	[[Category: Inhibitor complex]]
		+	[[Category: Ppi with p53]]

OCA at 04:12, 16 May 2018

OCA — Wed, 16 May 2018 04:12:31 GMT

←Older revision		Revision as of 04:12, 16 May 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ggn is ON HOLD	+	The entry 6ggn is ON HOLD until Paper Publication

	Authors: Kallen, J.		Authors: Kallen, J.

OCA: Protected "6ggn" [edit=sysop:move=sysop]

OCA — Wed, 09 May 2018 05:08:33 GMT

Protected "6ggn" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:08, 9 May 2018

OCA: New page: '''Unreleased structure''' The entry 6ggn is ON HOLD Authors: Kallen, J. Description: In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor [[Category: Unr...

OCA — Wed, 09 May 2018 05:08:32 GMT

New page: '''Unreleased structure''' The entry 6ggn is ON HOLD Authors: Kallen, J. Description: In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor [[Category: Unr...

New page

'''Unreleased structure'''

The entry 6ggn is ON HOLD

Authors: Kallen, J.

Description: In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor
[[Category: Unreleased Structures]]
[[Category: Kallen, J]]