OCA at 08:07, 22 May 2024

2024-05-22T08:07:31Z

←Older revision		Revision as of 08:07, 22 May 2024
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8wtr is ~~ON HOLD until Paper~~ Publication	+	==HUMAN SQUALENE SYNTHASE IN COMPLEX WITH (1S,3R)-3-[2-Chloro-5-(2,2-dimethyl-propyl)-13-(2-methoxy-phenyl)-6,8-dioxo-5,6,7,8,10,11-hexahydro-13H-12-oxa-5,9-diaza-benzocycloundecen-9-yl]-cyclohexanecarboxylic acid==
		+	<StructureSection load='8wtr' size='340' side='right'caption='[[8wtr]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8wtr]] 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=8WTR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WTR 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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KV3:(1~{S},3~{R})-3-[(10~{S})-13-chloranyl-2-(2,2-dimethylpropyl)-10-(2-methoxyphenyl)-3,5-bis(oxidanylidene)-9-oxa-2,6-diazabicyclo[9.4.0]pentadeca-1(15),11,13-trien-6-yl]cyclohexane-1-carboxylic+acid'>KV3</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=8wtr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wtr OCA], [https://pdbe.org/8wtr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wtr RCSB], [https://www.ebi.ac.uk/pdbsum/8wtr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wtr ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/FDFT_HUMAN FDFT_HUMAN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Squalene synthase is one of the most promising pharmaceutical targets to treat hyperlipidemia. Inhibition of the squalene synthase causes a decrease in the hepatic cholesterol concentration. We have already reported the design and synthesis of highly potent benzhydrol-type squalene inhibitors. Although these templates showed unique and potent cyclic active conformations via intramolecular hydrogen bonds, the in vivo cholesterol-lowering efficacy was insufficient. We attempted to improve their potential as an orally active medicine. In our medicinal chemistry effort, cyclized 11-membered ring templates were acquired. The novel series of compounds exhibited potent squalene synthase inhibitory activity, and one of the derivatives, isomer A-(1S, 3R)-14i, showed plasma lipid-lowering efficacy in hamster and marmoset repeated-dose studies. Our findings provide valuable insights into the design and development of novel and unique 11-membered ring-type highly potent squalene synthase inhibitors.

-	~~Authors: Suzuki, M~~., Haginoya, N., Suzuki, M., Ishigai, Y., Terayama, K., Kanda, A., Sugita, K.	+	Discovery of Novel 11-Membered Templates as Squalene Synthase Inhibitors.,Haginoya N, Suzuki M, Suzuki M, Ishigai Y, Terayama K, Kanda A, Sugita K J Med Chem. 2024 Apr 11;67(7):5305-5314. doi: 10.1021/acs.jmedchem.3c01500. Epub , 2024 Mar 22. PMID:38517948<ref>PMID:38517948</ref>

-	~~Description: HUMAN SQUALENE SYNTHASE IN COMPLEX WITH (1S~~,~~3R)~~-3-[~~2-Chloro-5-(2,2-dimethyl-propyl)-13-(2-methoxy-phenyl)-6,8-dioxo-5,6,7,8,10,11-hexahydro-13H-12-oxa-5,9-diaza-benzocycloundecen-9-yl~~]~~-cyclohexanecarboxylic acid~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Sugita, K~~]]	+	<div class="pdbe-citations 8wtr" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Suzuki, M~~]]	+	== References ==
-	[[Category: ~~Terayama, K~~]]	+	<references/>
-	[[Category: ~~Ishigai, Y~~]]	+	__TOC__
-	[[Category: ~~Haginoya, N~~]]	+	</StructureSection>
-	[[Category: ~~Kanda, A~~]]	+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Haginoya N]]
		+	[[Category: Ishigai Y]]
		+	[[Category: Kanda A]]
		+	[[Category: Sugita K]]
		+	[[Category: Suzuki M]]
		+	[[Category: Terayama K]]

OCA at 07:10, 6 December 2023

2023-12-06T07:10:07Z

←Older revision		Revision as of 07:10, 6 December 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8wtr is ON HOLD	+	The entry 8wtr is ON HOLD until Paper Publication

	Authors: Suzuki, M., Haginoya, N., Suzuki, M., Ishigai, Y., Terayama, K., Kanda, A., Sugita, K.		Authors: Suzuki, M., Haginoya, N., Suzuki, M., Ishigai, Y., Terayama, K., Kanda, A., Sugita, K.

OCA: Protected "8wtr" [edit=sysop:move=sysop]

2023-10-25T06:11:03Z

Protected "8wtr" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:11, 25 October 2023

OCA: New page: '''Unreleased structure''' The entry 8wtr is ON HOLD Authors: Suzuki, M., Haginoya, N., Suzuki, M., Ishigai, Y., Terayama, K., Kanda, A., Sugita, K. Description: HUMAN SQUALENE SYNTHAS...

2023-10-25T06:11:02Z

New page: '''Unreleased structure''' The entry 8wtr is ON HOLD Authors: Suzuki, M., Haginoya, N., Suzuki, M., Ishigai, Y., Terayama, K., Kanda, A., Sugita, K. Description: HUMAN SQUALENE SYNTHAS...

New page

'''Unreleased structure'''

The entry 8wtr is ON HOLD

Authors: Suzuki, M., Haginoya, N., Suzuki, M., Ishigai, Y., Terayama, K., Kanda, A., Sugita, K.

Description: HUMAN SQUALENE SYNTHASE IN COMPLEX WITH (1S,3R)-3-[2-Chloro-5-(2,2-dimethyl-propyl)-13-(2-methoxy-phenyl)-6,8-dioxo-5,6,7,8,10,11-hexahydro-13H-12-oxa-5,9-diaza-benzocycloundecen-9-yl]-cyclohexanecarboxylic acid
[[Category: Unreleased Structures]]
[[Category: Sugita, K]]
[[Category: Suzuki, M]]
[[Category: Terayama, K]]
[[Category: Ishigai, Y]]
[[Category: Haginoya, N]]
[[Category: Kanda, A]]

8wtr - Revision history

OCA at 08:07, 22 May 2024

OCA at 07:10, 6 December 2023

OCA: Protected "8wtr" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8wtr is ON HOLD Authors: Suzuki, M., Haginoya, N., Suzuki, M., Ishigai, Y., Terayama, K., Kanda, A., Sugita, K. Description: HUMAN SQUALENE SYNTHAS...