7l50 - Revision history

OCA at 15:37, 18 October 2023

OCA — Wed, 18 Oct 2023 15:37:56 GMT

←Older revision		Revision as of 15:37, 18 October 2023
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	<StructureSection load='7l50' size='340' side='right'caption='[[7l50]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='7l50' size='340' side='right'caption='[[7l50]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7l50]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L50 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7l50]] is a 4 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=7L50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L50 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=XOM:(2s,4R)-2-{3-[(3-chloro-4-methylphenyl)methoxy]azetidine-1-carbonyl}-7-oxa-5-azaspiro[3.4]octan-6-one'>XOM</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.3Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MGLL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=XOM:(2s,4R)-2-{3-[(3-chloro-4-methylphenyl)methoxy]azetidine-1-carbonyl}-7-oxa-5-azaspiro[3.4]octan-6-one'>XOM</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=7l50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l50 OCA], [https://pdbe.org/7l50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l50 RCSB], [https://www.ebi.ac.uk/pdbsum/7l50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l50 ProSAT]</span></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=7l50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l50 OCA], [https://pdbe.org/7l50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l50 RCSB], [https://www.ebi.ac.uk/pdbsum/7l50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l50 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/MGLL_HUMAN MGLL_HUMAN] Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (By similarity). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth.<ref>PMID:20079333</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 17:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 7l50" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7l50" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Lipase 3D Structures\|Lipase 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lane, W]]	+	[[Category: Lane W]]
-	[[Category: Qin, L]]	+	[[Category: Qin L]]
-	[[Category: Skene~~, R J]]~~	+	[[Category: Skene RJ]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-inhibitor complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Serine hydrolase~~]]	+

OCA at 09:36, 15 September 2021

OCA — Wed, 15 Sep 2021 09:36:24 GMT

←Older revision		Revision as of 09:36, 15 September 2021
Line 1:		Line 1:

-	==Crystal structure of human monoacylglycerol lipase in complex with compound 1==	+	==Crystal structure of human monoacylglycerol lipase in complex with compound 4f==
	<StructureSection load='7l50' size='340' side='right'caption='[[7l50]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='7l50' size='340' side='right'caption='[[7l50]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==

OCA at 06:32, 25 August 2021

OCA — Wed, 25 Aug 2021 06:32:01 GMT

←Older revision		Revision as of 06:32, 25 August 2021
Line 1:		Line 1:

	==Crystal structure of human monoacylglycerol lipase in complex with compound 1==		==Crystal structure of human monoacylglycerol lipase in complex with compound 1==
-	<StructureSection load='7l50' size='340' side='right'caption='[[7l50]]' scene=''>	+	<StructureSection load='7l50' size='340' side='right'caption='[[7l50]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L50 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7l50]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L50 FirstGlance]. <br>
-	</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=7l50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l50 OCA], [https://pdbe.org/7l50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l50 RCSB], [https://www.ebi.ac.uk/pdbsum/7l50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l50 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=XOM:(2s,4R)-2-{3-[(3-chloro-4-methylphenyl)methoxy]azetidine-1-carbonyl}-7-oxa-5-azaspiro[3.4]octan-6-one'>XOM</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MGLL ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7l50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l50 OCA], [https://pdbe.org/7l50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l50 RCSB], [https://www.ebi.ac.uk/pdbsum/7l50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l50 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The therapeutic potential of monoacylglycerol lipase (MAGL) inhibitors in central nervous system-related diseases has attracted attention worldwide. However, the availability of reversible-type inhibitor is still limited to clarify the pharmacological effect. Herein, we report the discovery of novel spiro chemical series as potent and reversible MAGL inhibitors with a different binding mode to MAGL using Arg57 and His121. Starting from hit compound 1 and its co-crystal structure with MAGL, structure-based drug discovery (SBDD) approach enabled us to generate various spiro scaffolds like 2a (azetidine-lactam), 2b (cyclobutane-lactam), and 2d (cyclobutane-carbamate) as novel bioisosteres of 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl moiety in 1 with higher lipophilic ligand efficiency (LLE). Optimization of the left hand side afforded 4f as a promising reversible MAGL inhibitor, which showed potent in vitro MAGL inhibitory activity (IC50 6.2 nM), good oral absorption, blood-brain barrier penetration, and significant pharmacodynamic changes (2-arachidonoylglycerol increase and arachidonic acid decrease) at 0.3-10 mg/kg, po. in mice.
		+
		+	Design and Synthesis of Novel Spiro Derivatives as Potent and Reversible Monoacylglycerol Lipase (MAGL) Inhibitors: Bioisosteric Transformation from 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl Moiety.,Ikeda S, Sugiyama H, Tokuhara H, Murakami M, Nakamura M, Oguro Y, Aida J, Morishita N, Sogabe S, Dougan DR, Gay SC, Qin L, Arimura N, Takahashi Y, Sasaki M, Kamada Y, Aoyama K, Kimoto K, Kamata M J Med Chem. 2021 Jul 30. doi: 10.1021/acs.jmedchem.1c00432. PMID:34328319<ref>PMID:34328319</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7l50" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lane W]]	+	[[Category: Lane, W]]
-	[[Category: Qin L]]	+	[[Category: Qin, L]]
-	[[Category: Skene RJ]]	+	[[Category: Skene, R J]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-inhibitor complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Serine hydrolase]]

OCA at 06:07, 11 August 2021

OCA — Wed, 11 Aug 2021 06:07:02 GMT

←Older revision		Revision as of 06:07, 11 August 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7l50 ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of human monoacylglycerol lipase in complex with compound 1==
-		+	<StructureSection load='7l50' size='340' side='right'caption='[[7l50]]' scene=''>
-	~~Authors~~: ~~Qin~~, L., ~~Lane~~, W., ~~Skene~~, R.J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L50 FirstGlance]. <br>
-	~~Description: Crystal structure of human monoacylglycerol lipase in complex with compound 1~~	+	</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=7l50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l50 OCA], [https://pdbe.org/7l50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l50 RCSB], [https://www.ebi.ac.uk/pdbsum/7l50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l50 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Lane, W]]	+	__TOC__
-	[[Category: Qin, L]]	+	</StructureSection>
-	[[Category: Skene~~, R.J~~]]	+	[[Category: Large Structures]]
		+	[[Category: Lane W]]
		+	[[Category: Qin L]]
		+	[[Category: Skene RJ]]

OCA at 06:44, 27 January 2021

OCA — Wed, 27 Jan 2021 06:44:35 GMT

←Older revision		Revision as of 06:44, 27 January 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7l50 is ON HOLD	+	The entry 7l50 is ON HOLD until Paper Publication

	Authors: Qin, L., Lane, W., Skene, R.J.		Authors: Qin, L., Lane, W., Skene, R.J.

OCA: Protected "7l50" [edit=sysop:move=sysop]

OCA — Wed, 30 Dec 2020 05:30:54 GMT

Protected "7l50" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:30, 30 December 2020

OCA: New page: '''Unreleased structure''' The entry 7l50 is ON HOLD Authors: Qin, L., Lane, W., Skene, R.J. Description: Crystal structure of human monoacylglycerol lipase in complex with compound 1 ...

OCA — Wed, 30 Dec 2020 05:30:53 GMT

New page: '''Unreleased structure''' The entry 7l50 is ON HOLD Authors: Qin, L., Lane, W., Skene, R.J. Description: Crystal structure of human monoacylglycerol lipase in complex with compound 1 ...

New page

'''Unreleased structure'''

The entry 7l50 is ON HOLD

Authors: Qin, L., Lane, W., Skene, R.J.

Description: Crystal structure of human monoacylglycerol lipase in complex with compound 1
[[Category: Unreleased Structures]]
[[Category: Lane, W]]
[[Category: Qin, L]]
[[Category: Skene, R.J]]