4btu - Revision history

OCA at 07:17, 1 May 2024

OCA — Wed, 01 May 2024 07:17:59 GMT

←Older revision		Revision as of 07:17, 1 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4btu]] 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=4BTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTU FirstGlance]. <br>		<table><tr><td colspan='2'>[[4btu]] 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=4BTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6XS:5-CHLORO-THIOPHENE-2-CARBOXYLIC+ACID+[(S)-2-[2-CHLORO-5-FLUORO-3-(2-OXO-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-3-(4-METHYL-PIPERAZIN-1-YL)-3-OXO-PROPYL]-AMIDE'>6XS</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 2.37Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6XS:5-CHLORO-THIOPHENE-2-CARBOXYLIC+ACID+[(S)-2-[2-CHLORO-5-FLUORO-3-(2-OXO-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-3-(4-METHYL-PIPERAZIN-1-YL)-3-OXO-PROPYL]-AMIDE'>6XS</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=4btu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btu OCA], [https://pdbe.org/4btu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btu RCSB], [https://www.ebi.ac.uk/pdbsum/4btu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btu 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=4btu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btu OCA], [https://pdbe.org/4btu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btu RCSB], [https://www.ebi.ac.uk/pdbsum/4btu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btu ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[https://omim.org/entry/227600 227600]]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>	+	[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[https://omim.org/entry/227600 227600]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.	+	[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

	==See Also==		==See Also==

OCA at 17:07, 7 September 2022

OCA — Wed, 07 Sep 2022 17:07:39 GMT

←Older revision		Revision as of 17:07, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='4btu' size='340' side='right'caption='[[4btu]], [[Resolution\|resolution]] 2.37Å' scene=''>		<StructureSection load='4btu' size='340' side='right'caption='[[4btu]], [[Resolution\|resolution]] 2.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4btu]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BTU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4btu]] 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=4BTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6XS:5-CHLORO-THIOPHENE-2-CARBOXYLIC+ACID+[(S)-2-[2-CHLORO-5-FLUORO-3-(2-OXO-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-3-(4-METHYL-PIPERAZIN-1-YL)-3-OXO-PROPYL]-AMIDE'>6XS</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6XS:5-CHLORO-THIOPHENE-2-CARBOXYLIC+ACID+[(S)-2-[2-CHLORO-5-FLUORO-3-(2-OXO-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-3-(4-METHYL-PIPERAZIN-1-YL)-3-OXO-PROPYL]-AMIDE'>6XS</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bti\|4bti]], [[4btt\|4btt]]</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=4btu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btu OCA], [https://pdbe.org/4btu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btu RCSB], [https://www.ebi.ac.uk/pdbsum/4btu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btu ProSAT]</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_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] </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=4btu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btu OCA], [~~http~~://pdbe.org/4btu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4btu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4btu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4btu ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[~~http~~://omim.org/entry/227600 227600]]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>	+	[[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[https://omim.org/entry/227600 227600]]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.	+	[[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 muM, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene P1 fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with Ki's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 muM) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.	+
-		+
-	5-Chlorothiophene-2-carboxylic Acid [(S)-2-[2-Methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperaz in-1-yl)-3-oxopropyl]amide (SAR107375), a Selective and Potent Orally Active Dual Thrombin and Factor Xa Inhibitor.,Meneyrol J, Follmann M, Lassalle G, Wehner V, Barre G, Rousseaux T, Altenburger JM, Petit F, Bocskei Z, Schreuder H, Alet N, Herault JP, Millet L, Dol F, Florian P, Schaeffer P, Sadoun F, Klieber S, Briot C, Bono F, Herbert JM J Med Chem. 2013 Dec 3. PMID:24175584<ref>PMID:24175584</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4btu" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 29:		Line 18:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Coagulation factor Xa]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Alet, N]]	+	[[Category: Alet N]]
-	[[Category: Altenburger~~, J M~~]]	+	[[Category: Altenburger JM]]
-	[[Category: Barre, G]]	+	[[Category: Barre G]]
-	[[Category: Bocskei, Z]]	+	[[Category: Bocskei Z]]
-	[[Category: Bono, F]]	+	[[Category: Bono F]]
-	[[Category: Briot, C]]	+	[[Category: Briot C]]
-	[[Category: Dol, F]]	+	[[Category: Dol F]]
-	[[Category: Follmann, M]]	+	[[Category: Follmann M]]
-	[[Category: Hasbrand, C]]	+	[[Category: Hasbrand C]]
-	[[Category: Herault, J P]]	+	[[Category: Herault J-P]]
-	[[Category: Herbert, J M]]	+	[[Category: Herbert J-M]]
-	[[Category: Klieber, S]]	+	[[Category: Klieber S]]
-	[[Category: Lassalle, G]]	+	[[Category: Lassalle G]]
-	[[Category: Meneyrol, J]]	+	[[Category: Meneyrol J]]
-	[[Category: Millet, L]]	+	[[Category: Millet L]]
-	[[Category: Petit, F]]	+	[[Category: Petit F]]
-	[[Category: Rousseaux, T]]	+	[[Category: Rousseaux T]]
-	[[Category: Sadoun, F]]	+	[[Category: Sadoun F]]
-	[[Category: Schaeffer, P]]	+	[[Category: Schaeffer P]]
-	[[Category: Schreuder, H]]	+	[[Category: Schreuder H]]
-	[[Category: Stehlin-Gaon, C]]	+	[[Category: Stehlin-Gaon C]]
-	[[Category: Wehner, V]]	+	[[Category: Wehner V]]
-	~~[[Category: Chlorothiophene p1 fragment]]~~	+
-	~~[[Category: Dual inhibitor]]~~	+
-	~~[[Category: Factor xa inhibitor]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Iv antithrombotic]]~~	+
-	~~[[Category: Microsomes stability]]~~	+
-	~~[[Category: Oral antithrombotic]]~~	+
-	~~[[Category: S3 subsite]]~~	+
-	~~[[Category: Sar107375]]~~	+
-	~~[[Category: Thrombin inhibitor~~]]	+

OCA at 13:51, 13 March 2019

OCA — Wed, 13 Mar 2019 13:51:38 GMT

←Older revision		Revision as of 13:51, 13 March 2019
Line 1:		Line 1:

-	==~~factor~~ Xa in complex with the dual thrombin-FXa inhibitor 57.==	+	==Factor Xa in complex with the dual thrombin-FXa inhibitor 57.==
-	<StructureSection load='4btu' size='340' side='right' caption='[[4btu]], [[Resolution\|resolution]] 2.37Å' scene=''>	+	<StructureSection load='4btu' size='340' side='right'caption='[[4btu]], [[Resolution\|resolution]] 2.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4btu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTU FirstGlance]. <br>		<table><tr><td colspan='2'>[[4btu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTU FirstGlance]. <br>
Line 31:		Line 31:
	[[Category: Coagulation factor Xa]]		[[Category: Coagulation factor Xa]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Alet, N]]		[[Category: Alet, N]]
	[[Category: Altenburger, J M]]		[[Category: Altenburger, J M]]

OCA at 00:55, 5 August 2016

OCA — Fri, 05 Aug 2016 00:55:01 GMT

←Older revision		Revision as of 00:55, 5 August 2016
Line 1:		Line 1:
		+
	==factor Xa in complex with the dual thrombin-FXa inhibitor 57.==		==factor Xa in complex with the dual thrombin-FXa inhibitor 57.==
	<StructureSection load='4btu' size='340' side='right' caption='[[4btu]], [[Resolution\|resolution]] 2.37Å' scene=''>		<StructureSection load='4btu' size='340' side='right' caption='[[4btu]], [[Resolution\|resolution]] 2.37Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bti\|4bti]], [[4btt\|4btt]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bti\|4bti]], [[4btt\|4btt]]</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_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] </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_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] </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=4btu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btu RCSB], [http://www.ebi.ac.uk/pdbsum/4btu 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=4btu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btu OCA], [http://pdbe.org/4btu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4btu RCSB], [http://www.ebi.ac.uk/pdbsum/4btu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4btu 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 4btu" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Factor Xa\|Factor Xa]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:27, 21 December 2014

OCA — Sun, 21 Dec 2014 17:27:24 GMT

←Older revision		Revision as of 17:27, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4btu\| PDB=4btu \| SCENE= }}~~	+	==factor Xa in complex with the dual thrombin-FXa inhibitor 57.==
-	===factor Xa in complex with the dual thrombin-FXa inhibitor 57.===	+	<StructureSection load='4btu' size='340' side='right' caption='[[4btu]], [[Resolution\|resolution]] 2.37Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24175584}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4btu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTU FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6XS:5-CHLORO-THIOPHENE-2-CARBOXYLIC+ACID+[(S)-2-[2-CHLORO-5-FLUORO-3-(2-OXO-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-3-(4-METHYL-PIPERAZIN-1-YL)-3-OXO-PROPYL]-AMIDE'>6XS</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bti\|4bti]], [[4btt\|4btt]]</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_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] </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=4btu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btu RCSB], [http://www.ebi.ac.uk/pdbsum/4btu PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[http://omim.org/entry/227600 227600]]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>		[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[http://omim.org/entry/227600 227600]]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>
-		+	== Function ==
-	==Function==	+
	[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.		[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 muM, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene P1 fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with Ki's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 muM) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.

-	~~==About this Structure==~~	+	5-Chlorothiophene-2-carboxylic Acid [(S)-2-[2-Methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperaz in-1-yl)-3-oxopropyl]amide (SAR107375), a Selective and Potent Orally Active Dual Thrombin and Factor Xa Inhibitor.,Meneyrol J, Follmann M, Lassalle G, Wehner V, Barre G, Rousseaux T, Altenburger JM, Petit F, Bocskei Z, Schreuder H, Alet N, Herault JP, Millet L, Dol F, Florian P, Schaeffer P, Sadoun F, Klieber S, Briot C, Bono F, Herbert JM J Med Chem. 2013 Dec 3. PMID:24175584<ref>PMID:24175584</ref>
-	[[~~4btu~~]] is a ~~4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~:/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4BTU OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024175584</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Coagulation factor Xa]]		[[Category: Coagulation factor Xa]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Alet, N.]]	+	[[Category: Alet, N]]
-	[[Category: Altenburger, J M.]]	+	[[Category: Altenburger, J M]]
-	[[Category: Barre, G.]]	+	[[Category: Barre, G]]
-	[[Category: Bocskei, Z.]]	+	[[Category: Bocskei, Z]]
-	[[Category: Bono, F.]]	+	[[Category: Bono, F]]
-	[[Category: Briot, C.]]	+	[[Category: Briot, C]]
-	[[Category: Dol, F.]]	+	[[Category: Dol, F]]
-	[[Category: Follmann, M.]]	+	[[Category: Follmann, M]]
-	[[Category: Hasbrand, C.]]	+	[[Category: Hasbrand, C]]
-	[[Category: Herault, J P.]]	+	[[Category: Herault, J P]]
-	[[Category: Herbert, J M.]]	+	[[Category: Herbert, J M]]
-	[[Category: Klieber, S.]]	+	[[Category: Klieber, S]]
-	[[Category: Lassalle, G.]]	+	[[Category: Lassalle, G]]
-	[[Category: Meneyrol, J.]]	+	[[Category: Meneyrol, J]]
-	[[Category: Millet, L.]]	+	[[Category: Millet, L]]
-	[[Category: Petit, F.]]	+	[[Category: Petit, F]]
-	[[Category: Rousseaux, T.]]	+	[[Category: Rousseaux, T]]
-	[[Category: Sadoun, F.]]	+	[[Category: Sadoun, F]]
-	[[Category: Schaeffer, P.]]	+	[[Category: Schaeffer, P]]
-	[[Category: Schreuder, H.]]	+	[[Category: Schreuder, H]]
-	[[Category: Stehlin-Gaon, C.]]	+	[[Category: Stehlin-Gaon, C]]
-	[[Category: Wehner, V.]]	+	[[Category: Wehner, V]]
	[[Category: Chlorothiophene p1 fragment]]		[[Category: Chlorothiophene p1 fragment]]
	[[Category: Dual inhibitor]]		[[Category: Dual inhibitor]]

OCA at 10:21, 18 December 2013

OCA — Wed, 18 Dec 2013 10:21:58 GMT

←Older revision		Revision as of 10:21, 18 December 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4btu\| PDB=4btu \| SCENE= }}
		+	===factor Xa in complex with the dual thrombin-FXa inhibitor 57.===
		+	{{ABSTRACT_PUBMED_24175584}}

-	~~The~~ entry ~~4btu is ON HOLD~~ ~~until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[http://omim.org/entry/227600 227600]]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>

-	~~Authors~~: ~~Meneyrol, J~~.~~, Follmann, M~~.~~, Lassalle, G., Wehner, V., Barre, G., Rousseaux, T., Altenburger, J.M., Petit, F., Bocskei, Z., Stehlin~~-~~Gaon~~, ~~C., Schreuder, H., Alet, N., Herault, J.-P., Millet, L., Dol, F., Hasbrand, C., Schaeffer, P., Sadoun, F., Klieber, S., Briot, C., Bono, F., Herbert, J.-M~~.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

-	~~Description~~: factor Xa ~~in complex with the dual thrombin~~-~~FXa inhibitor 57~~.	+	==About this Structure==
		+	[[4btu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTU OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:024175584</ref><references group="xtra"/><references/>
		+	[[Category: Coagulation factor Xa]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Alet, N.]]
		+	[[Category: Altenburger, J M.]]
		+	[[Category: Barre, G.]]
		+	[[Category: Bocskei, Z.]]
		+	[[Category: Bono, F.]]
		+	[[Category: Briot, C.]]
		+	[[Category: Dol, F.]]
		+	[[Category: Follmann, M.]]
		+	[[Category: Hasbrand, C.]]
		+	[[Category: Herault, J P.]]
		+	[[Category: Herbert, J M.]]
		+	[[Category: Klieber, S.]]
		+	[[Category: Lassalle, G.]]
		+	[[Category: Meneyrol, J.]]
		+	[[Category: Millet, L.]]
		+	[[Category: Petit, F.]]
		+	[[Category: Rousseaux, T.]]
		+	[[Category: Sadoun, F.]]
		+	[[Category: Schaeffer, P.]]
		+	[[Category: Schreuder, H.]]
		+	[[Category: Stehlin-Gaon, C.]]
		+	[[Category: Wehner, V.]]
		+	[[Category: Chlorothiophene p1 fragment]]
		+	[[Category: Dual inhibitor]]
		+	[[Category: Factor xa inhibitor]]
		+	[[Category: Hydrolase]]
		+	[[Category: Iv antithrombotic]]
		+	[[Category: Microsomes stability]]
		+	[[Category: Oral antithrombotic]]
		+	[[Category: S3 subsite]]
		+	[[Category: Sar107375]]
		+	[[Category: Thrombin inhibitor]]

OCA at 09:15, 27 November 2013

OCA — Wed, 27 Nov 2013 09:15:54 GMT

←Older revision		Revision as of 09:15, 27 November 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4btu is ON HOLD	+	The entry 4btu is ON HOLD until Paper Publication

	Authors: Meneyrol, J., Follmann, M., Lassalle, G., Wehner, V., Barre, G., Rousseaux, T., Altenburger, J.M., Petit, F., Bocskei, Z., Stehlin-Gaon, C., Schreuder, H., Alet, N., Herault, J.-P., Millet, L., Dol, F., Hasbrand, C., Schaeffer, P., Sadoun, F., Klieber, S., Briot, C., Bono, F., Herbert, J.-M.		Authors: Meneyrol, J., Follmann, M., Lassalle, G., Wehner, V., Barre, G., Rousseaux, T., Altenburger, J.M., Petit, F., Bocskei, Z., Stehlin-Gaon, C., Schreuder, H., Alet, N., Herault, J.-P., Millet, L., Dol, F., Hasbrand, C., Schaeffer, P., Sadoun, F., Klieber, S., Briot, C., Bono, F., Herbert, J.-M.

	Description: factor Xa in complex with the dual thrombin-FXa inhibitor 57.		Description: factor Xa in complex with the dual thrombin-FXa inhibitor 57.

OCA at 07:35, 21 August 2013

OCA — Wed, 21 Aug 2013 07:35:41 GMT

←Older revision		Revision as of 07:35, 21 August 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4btu is ON HOLD ~~until Paper Publication~~	+	The entry 4btu is ON HOLD

	Authors: Meneyrol, J., Follmann, M., Lassalle, G., Wehner, V., Barre, G., Rousseaux, T., Altenburger, J.M., Petit, F., Bocskei, Z., Stehlin-Gaon, C., Schreuder, H., Alet, N., Herault, J.-P., Millet, L., Dol, F., Hasbrand, C., Schaeffer, P., Sadoun, F., Klieber, S., Briot, C., Bono, F., Herbert, J.-M.		Authors: Meneyrol, J., Follmann, M., Lassalle, G., Wehner, V., Barre, G., Rousseaux, T., Altenburger, J.M., Petit, F., Bocskei, Z., Stehlin-Gaon, C., Schreuder, H., Alet, N., Herault, J.-P., Millet, L., Dol, F., Hasbrand, C., Schaeffer, P., Sadoun, F., Klieber, S., Briot, C., Bono, F., Herbert, J.-M.

	Description: factor Xa in complex with the dual thrombin-FXa inhibitor 57.		Description: factor Xa in complex with the dual thrombin-FXa inhibitor 57.

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

OCA — Sun, 30 Jun 2013 08:29:54 GMT

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

←Older revision

Revision as of 08:29, 30 June 2013

OCA: New page: '''Unreleased structure''' The entry 4btu is ON HOLD until Paper Publication Authors: Meneyrol, J., Follmann, M., Lassalle, G., Wehner, V., Barre, G., Rousseaux, T., Altenburger, J.M., ...

OCA — Sun, 30 Jun 2013 08:29:53 GMT

New page: '''Unreleased structure''' The entry 4btu is ON HOLD until Paper Publication Authors: Meneyrol, J., Follmann, M., Lassalle, G., Wehner, V., Barre, G., Rousseaux, T., Altenburger, J.M., ...

New page

'''Unreleased structure'''

The entry 4btu is ON HOLD until Paper Publication

Authors: Meneyrol, J., Follmann, M., Lassalle, G., Wehner, V., Barre, G., Rousseaux, T., Altenburger, J.M., Petit, F., Bocskei, Z., Stehlin-Gaon, C., Schreuder, H., Alet, N., Herault, J.-P., Millet, L., Dol, F., Hasbrand, C., Schaeffer, P., Sadoun, F., Klieber, S., Briot, C., Bono, F., Herbert, J.-M.

Description: factor Xa in complex with the dual thrombin-FXa inhibitor 57.