2phb

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{{Seed}}
 
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[[Image:2phb.png|left|200px]]
 
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==An Orally Efficacious Factor Xa Inhibitor==
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The line below this paragraph, containing "STRUCTURE_2phb", creates the "Structure Box" on the page.
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<StructureSection load='2phb' size='340' side='right'caption='[[2phb]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2phb]] 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=2PHB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PHB FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=230:(2R,4R)-N~1~-(4-CHLOROPHENYL)-N~2~-[2-FLUORO-4-(2-OXOPYRIDIN-1(2H)-YL)PHENYL]-4-METHOXYPYRROLIDINE-1,2-DICARBOXAMIDE'>230</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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{{STRUCTURE_2phb| PDB=2phb | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2phb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2phb OCA], [https://pdbe.org/2phb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2phb RCSB], [https://www.ebi.ac.uk/pdbsum/2phb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2phb ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ph/2phb_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2phb ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Herein, we report the discovery of novel, proline-based factor Xa inhibitors containing a neutral P1 chlorophenyl pharmacophore. Through the additional incorporation of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one 22, as a P4 pharmacophore, we discovered compound 7 (PD 0348292). This compound is a selective, orally bioavailable, efficacious FXa inhibitor that is currently in phase II clinical trials for the treatment and prevention of thrombotic disorders.
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===An Orally Efficacious Factor Xa Inhibitor===
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The discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarb oxamide (PD 0348292), an orally efficacious factor Xa inhibitor.,Kohrt JT, Bigge CF, Bryant JW, Casimiro-Garcia A, Chi L, Cody WL, Dahring T, Dudley DA, Filipski KJ, Haarer S, Heemstra R, Janiczek N, Narasimhan L, McClanahan T, Peterson JT, Sahasrabudhe V, Schaum R, Van Huis CA, Welch KM, Zhang E, Leadley RJ, Edmunds JJ Chem Biol Drug Des. 2007 Aug;70(2):100-12. PMID:17683371<ref>PMID:17683371</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2phb" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17683371}}, adds the Publication Abstract to the page
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*[[Factor Xa|Factor Xa]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17683371 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17683371}}
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]]
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==About this Structure==
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2PHB is a [[Protein complex]] structure of sequences 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=2PHB OCA].
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==Reference==
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The discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarb oxamide (PD 0348292), an orally efficacious factor Xa inhibitor., Kohrt JT, Bigge CF, Bryant JW, Casimiro-Garcia A, Chi L, Cody WL, Dahring T, Dudley DA, Filipski KJ, Haarer S, Heemstra R, Janiczek N, Narasimhan L, McClanahan T, Peterson JT, Sahasrabudhe V, Schaum R, Van Huis CA, Welch KM, Zhang E, Leadley RJ, Edmunds JJ, Chem Biol Drug Des. 2007 Aug;70(2):100-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17683371 17683371]
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[[Category: Coagulation factor Xa]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Bigge, C F.]]
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[[Category: Bigge CF]]
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[[Category: Finzel, B C.]]
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[[Category: Finzel BC]]
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[[Category: Kohrt, J T.]]
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[[Category: Kohrt JT]]
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[[Category: Zhang, E.]]
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[[Category: Zhang E]]
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[[Category: Blood clotting]]
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[[Category: Fxa coagulation factor inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 18:48:30 2008''
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Current revision

An Orally Efficacious Factor Xa Inhibitor

PDB ID 2phb

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