4x6n - Revision history

OCA at 21:15, 12 April 2023

OCA — Wed, 12 Apr 2023 21:15:38 GMT

←Older revision		Revision as of 21:15, 12 April 2023
Line 3:		Line 3:
	<StructureSection load='4x6n' size='340' side='right'caption='[[4x6n]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='4x6n' size='340' side='right'caption='[[4x6n]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4x6n]] is a 2 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=4X6N OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4X6N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4x6n]] 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=4X6N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X6N FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Y5:1-{(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL}-3-[5-CHLORO-2-(1H-TETRAZOL-1-YL)BENZYL]UREA'>3Y5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3Y5:1-{(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL}-3-[5-CHLORO-2-(1H-TETRAZOL-1-YL)BENZYL]UREA'>3Y5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4x6m\|4x6m]], [[4x6o\|4x6o]], [[4x6p\|4x6p]]</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=4x6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6n OCA], [https://pdbe.org/4x6n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x6n RCSB], [https://www.ebi.ac.uk/pdbsum/4x6n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6n ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F11 ([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/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=4x6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6n OCA], [~~http~~://pdbe.org/4x6n PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4x6n RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4x6n PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6n ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[~~http~~://omim.org/entry/612416 612416]]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>	+	[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[https://omim.org/entry/612416 612416]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.	+	[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==See Also==		==See Also==
-	*[[Factor XIa\|Factor XIa]]	+	*[[Factor XIa 3D structures\|Factor XIa 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Coagulation factor XIa]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Wei, A]]	+	[[Category: Wei A]]
-	~~[[Category: Blood coagulation factor]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Protein inhibitor complex]]~~	+
-	~~[[Category: Serine protease~~]]	+

OCA at 07:26, 29 May 2019

OCA — Wed, 29 May 2019 07:26:28 GMT

←Older revision		Revision as of 07:26, 29 May 2019
Line 1:		Line 1:

	==FACTOR XIA IN COMPLEX WITH THE INHIBITOR 1-{(1S)-1-[4-(3-amino-1H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl}-3-[5-chloro-2-(1H-tetrazol-1-yl)benzyl]urea==		==FACTOR XIA IN COMPLEX WITH THE INHIBITOR 1-{(1S)-1-[4-(3-amino-1H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl}-3-[5-chloro-2-(1H-tetrazol-1-yl)benzyl]urea==
-	<StructureSection load='4x6n' size='340' side='right' caption='[[4x6n]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='4x6n' size='340' side='right'caption='[[4x6n]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4x6n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4x6n]] is a 2 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=4X6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6N FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Y5:1-{(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL}-3-[5-CHLORO-2-(1H-TETRAZOL-1-YL)BENZYL]UREA'>3Y5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Y5:1-{(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL}-3-[5-CHLORO-2-(1H-TETRAZOL-1-YL)BENZYL]UREA'>3Y5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4x6m\|4x6m]], [[4x6o\|4x6o]], [[4x6p\|4x6p]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4x6m\|4x6m]], [[4x6o\|4x6o]], [[4x6p\|4x6p]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F11 ([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/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=4x6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6n OCA], [http://pdbe.org/4x6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x6n RCSB], [http://www.ebi.ac.uk/pdbsum/4x6n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6n 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=4x6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6n OCA], [http://pdbe.org/4x6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x6n RCSB], [http://www.ebi.ac.uk/pdbsum/4x6n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6n ProSAT]</span></td></tr>
Line 30:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Coagulation factor XIa]]		[[Category: Coagulation factor XIa]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Wei, A]]		[[Category: Wei, A]]
	[[Category: Blood coagulation factor]]		[[Category: Blood coagulation factor]]

OCA at 00:15, 26 January 2017

OCA — Thu, 26 Jan 2017 00:15:11 GMT

←Older revision		Revision as of 00:15, 26 January 2017
Line 1:		Line 1:
		+
	==FACTOR XIA IN COMPLEX WITH THE INHIBITOR 1-{(1S)-1-[4-(3-amino-1H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl}-3-[5-chloro-2-(1H-tetrazol-1-yl)benzyl]urea==		==FACTOR XIA IN COMPLEX WITH THE INHIBITOR 1-{(1S)-1-[4-(3-amino-1H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl}-3-[5-chloro-2-(1H-tetrazol-1-yl)benzyl]urea==
	<StructureSection load='4x6n' size='340' side='right' caption='[[4x6n]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='4x6n' size='340' side='right' caption='[[4x6n]], [[Resolution\|resolution]] 2.10Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4x6m\|4x6m]], [[4x6o\|4x6o]], [[4x6p\|4x6p]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4x6m\|4x6m]], [[4x6o\|4x6o]], [[4x6p\|4x6p]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=4x6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4x6n RCSB], [http://www.ebi.ac.uk/pdbsum/4x6n PDBsum]</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=4x6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6n OCA], [http://pdbe.org/4x6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x6n RCSB], [http://www.ebi.ac.uk/pdbsum/4x6n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6n ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4x6n" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Factor XIa\|Factor XIa]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:05, 18 March 2015

OCA — Wed, 18 Mar 2015 12:05:30 GMT

←Older revision		Revision as of 12:05, 18 March 2015
Line 14:		Line 14:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~The~~ structure-~~activity relationships (SAR)~~ of ~~six-membered ring replacements for~~ the ~~imidazole ring scaffold is described. This work~~ led to the ~~discovery~~ of the ~~potent~~ and ~~selective pyridine (S)-23 and pyridinone (+/-)-24 factor XIa inhibitors~~. ~~SAR~~ and ~~X-ray crystal structure data highlight the key differences between imidazole and six-membered ring analogs~~.	+	Compound 2 was previously identified as a potent inhibitor of factor XIa lacking oral bioavailability. A structure-based approach was used to design analogs of 2 with novel P1 moieties with good selectivity profiles and oral bioavailability. Further optimization of the P1 group led to the identification of a 4-chlorophenyltetrazole P1 analog, which when combined with further modifications to the linker and P2' group provided compound 32 with FXIa Ki=6.7nM and modest oral exposure in dogs.

-	~~Pyridine and pyridinone~~-based factor XIa ~~inhibitors~~.,Corte JR, Fang T, ~~Hangeland JJ~~, ~~Friends TJ~~, Rendina AR~~, Luettgen JM~~, Bozarth JM, ~~Barbera FA, Rossi KA~~, Wei A, Ramamurthy V, Morin PE, Seiffert DA~~, Wexler RR~~, Quan ML Bioorg Med Chem Lett. ~~2014 Dec 31~~. pii: S0960-894X(14)~~01358~~-4. doi:, 10.1016/j.bmcl.~~2014~~.12.~~050~~. PMID:~~25592713~~<ref>PMID:~~25592713~~</ref>	+	Structure-based design of inhibitors of coagulation factor XIa with novel P1 moieties.,Pinto DJ, Smallheer JM, Corte JR, Austin EJ, Wang C, Fang T, Smith LM 2nd, Rossi KA, Rendina AR, Bozarth JM, Zhang G, Wei A, Ramamurthy V, Sheriff S, Myers JE Jr, Morin PE, Luettgen JM, Seiffert DA, Quan ML, Wexler RR Bioorg Med Chem Lett. 2015 Feb 4. pii: S0960-894X(15)00040-2. doi:, 10.1016/j.bmcl.2015.01.028. PMID:25728130<ref>PMID:25728130</ref>

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

OCA at 07:58, 25 February 2015

OCA — Wed, 25 Feb 2015 07:58:52 GMT

←Older revision		Revision as of 07:58, 25 February 2015
Line 14:		Line 14:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Antithrombotic agents that are inhibitors of factor XIa~~ (~~FXIa~~) ~~have~~ the ~~potential to demonstrate robust efficacy with a low bleeding risk profile~~. ~~Herein, we describe a series~~ of ~~tetrahydroquinoline (THQ) derivatives as FXIa inhibitors. Compound 1 was identified as a~~ potent and selective ~~tool compound for proof of concept studies. It exhibited excellent antithrombotic efficacy in rabbit thrombosis models~~ and ~~did not prolong bleeding times~~. ~~This demonstrates proof of concept for~~ the ~~FXIa mechanism in animal models with a reversible, small molecule inhibitor~~.	+	The structure-activity relationships (SAR) of six-membered ring replacements for the imidazole ring scaffold is described. This work led to the discovery of the potent and selective pyridine (S)-23 and pyridinone (+/-)-24 factor XIa inhibitors. SAR and X-ray crystal structure data highlight the key differences between imidazole and six-membered ring analogs.

-	~~Tetrahydroquinoline Derivatives as Potent~~ and ~~Selective Factor~~ XIa ~~Inhibitors~~.,~~Quan ML~~, ~~Wong PC~~, ~~Wang C~~, ~~Woerner F~~, ~~Smallheer JM~~, ~~Barbera FA~~, Bozarth JM, ~~Brown RL, Harpel MR, Luettgen JM, Morin PE, Peterson T, Ramamurthy V, Rendina AR~~, Rossi KA~~, Watson CA~~, Wei A, ~~Zhang G~~, Seiffert D, Wexler RR J Med Chem. 2014 ~~Jan 17~~. PMID:~~24405333~~<ref>PMID:~~24405333~~</ref>	+	Pyridine and pyridinone-based factor XIa inhibitors.,Corte JR, Fang T, Hangeland JJ, Friends TJ, Rendina AR, Luettgen JM, Bozarth JM, Barbera FA, Rossi KA, Wei A, Ramamurthy V, Morin PE, Seiffert DA, Wexler RR, Quan ML Bioorg Med Chem Lett. 2014 Dec 31. pii: S0960-894X(14)01358-4. doi:, 10.1016/j.bmcl.2014.12.050. PMID:25592713<ref>PMID:25592713</ref>

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

OCA at 13:00, 18 February 2015

OCA — Wed, 18 Feb 2015 13:00:08 GMT

←Older revision		Revision as of 13:00, 18 February 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==FACTOR XIA IN COMPLEX WITH THE INHIBITOR 1-{(1S)-1-[4-(3-amino-1H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl}-3-[5-chloro-2-(1H-tetrazol-1-yl)benzyl]urea==
		+	<StructureSection load='4x6n' size='340' side='right' caption='[[4x6n]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4x6n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6N FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Y5:1-{(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL}-3-[5-CHLORO-2-(1H-TETRAZOL-1-YL)BENZYL]UREA'>3Y5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4x6m\|4x6m]], [[4x6o\|4x6o]], [[4x6p\|4x6p]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=4x6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4x6n RCSB], [http://www.ebi.ac.uk/pdbsum/4x6n PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[http://omim.org/entry/612416 612416]]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Antithrombotic agents that are inhibitors of factor XIa (FXIa) have the potential to demonstrate robust efficacy with a low bleeding risk profile. Herein, we describe a series of tetrahydroquinoline (THQ) derivatives as FXIa inhibitors. Compound 1 was identified as a potent and selective tool compound for proof of concept studies. It exhibited excellent antithrombotic efficacy in rabbit thrombosis models and did not prolong bleeding times. This demonstrates proof of concept for the FXIa mechanism in animal models with a reversible, small molecule inhibitor.

-	~~The entry 4x6n is ON HOLD~~	+	Tetrahydroquinoline Derivatives as Potent and Selective Factor XIa Inhibitors.,Quan ML, Wong PC, Wang C, Woerner F, Smallheer JM, Barbera FA, Bozarth JM, Brown RL, Harpel MR, Luettgen JM, Morin PE, Peterson T, Ramamurthy V, Rendina AR, Rossi KA, Watson CA, Wei A, Zhang G, Seiffert D, Wexler RR J Med Chem. 2014 Jan 17. PMID:24405333<ref>PMID:24405333</ref>

-	~~Authors: Wei~~, A.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR 3-[(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL]-1-{[5-CHLORO-2-(1H-1,2,3,4-TETRAZOL-1-YL) PHENYL]METHYL}UREA~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Coagulation factor XIa]]
	[[Category: Wei, A]]		[[Category: Wei, A]]
		+	[[Category: Blood coagulation factor]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Protein inhibitor complex]]
		+	[[Category: Serine protease]]

OCA at 20:34, 24 December 2014

OCA — Wed, 24 Dec 2014 20:34:14 GMT

←Older revision		Revision as of 20:34, 24 December 2014
Line 6:		Line 6:

	Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR 3-[(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL]-1-{[5-CHLORO-2-(1H-1,2,3,4-TETRAZOL-1-YL) PHENYL]METHYL}UREA		Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR 3-[(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL]-1-{[5-CHLORO-2-(1H-1,2,3,4-TETRAZOL-1-YL) PHENYL]METHYL}UREA
		+	[[Category: Unreleased Structures]]
		+	[[Category: Wei, A]]

OCA: Protected "4x6n" [edit=sysop:move=sysop]

OCA — Wed, 17 Dec 2014 11:44:08 GMT

Protected "4x6n" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:44, 17 December 2014

OCA: New page: '''Unreleased structure''' The entry 4x6n is ON HOLD Authors: Wei, A. Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR 3-[(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-...

OCA — Wed, 17 Dec 2014 11:44:06 GMT

New page: '''Unreleased structure''' The entry 4x6n is ON HOLD Authors: Wei, A. Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR 3-[(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-...

New page

'''Unreleased structure'''

The entry 4x6n is ON HOLD

Authors: Wei, A.

Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR 3-[(1S)-1-[4-(3-AMINO-1H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL]-1-{[5-CHLORO-2-(1H-1,2,3,4-TETRAZOL-1-YL) PHENYL]METHYL}UREA