2wyg: Difference between revisions
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==STRUCTURE AND PROPERTY BASED DESIGN OF FACTOR XA INHIBITORS: PYRROLIDIN-2-ONES WITH MONOARYL P4 MOTIFS== | |||
<StructureSection load='2wyg' size='340' side='right' caption='[[2wyg]], [[Resolution|resolution]] 1.88Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2wyg]] is a 2 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=2WYG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WYG FirstGlance]. <br> | |||
==Disease== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=461:(E)-2-(5-CHLOROTHIOPHEN-2-YL)-N-[(3S)-1-{4-[(1R)-1-(DIMETHYLAMINO)ETHYL]-2-FLUOROPHENYL}-2-OXOPYRROLIDIN-3-YL]ETHENESULFONAMIDE'>461</scene></td></tr> | ||
[[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> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2j34|2j34]], [[1wu1|1wu1]], [[2bq7|2bq7]], [[2w3k|2w3k]], [[2vwo|2vwo]], [[1xka|1xka]], [[1nfw|1nfw]], [[2gd4|2gd4]], [[2vvv|2vvv]], [[1lpg|1lpg]], [[1msx|1msx]], [[2vvu|2vvu]], [[1p0s|1p0s]], [[2g00|2g00]], [[1mq6|1mq6]], [[1xkb|1xkb]], [[1iqe|1iqe]], [[1g2m|1g2m]], [[2vh0|2vh0]], [[1nfy|1nfy]], [[2uwl|2uwl]], [[2bok|2bok]], [[1hcg|1hcg]], [[1lpz|1lpz]], [[2w3i|2w3i]], [[1z6e|1z6e]], [[2jkh|2jkh]], [[2uwp|2uwp]], [[1g2l|1g2l]], [[1nfu|1nfu]], [[1fax|1fax]], [[2bq6|2bq6]], [[1iqf|1iqf]], [[1nl8|1nl8]], [[1iqg|1iqg]], [[1iqh|1iqh]], [[1lqd|1lqd]], [[2uwo|2uwo]], [[1c5m|1c5m]], [[1ioe|1ioe]], [[1f0s|1f0s]], [[1f0r|1f0r]], [[1mq5|1mq5]], [[2bmg|2bmg]], [[1iqn|1iqn]], [[2bqw|2bqw]], [[1iqm|1iqm]], [[1ezq|1ezq]], [[2vwl|2vwl]], [[2vh6|2vh6]], [[1fjs|1fjs]], [[1lpk|1lpk]], [[2j4i|2j4i]], [[1nfx|1nfx]], [[2vwn|2vwn]], [[1iqj|1iqj]], [[2j94|2j94]], [[2cji|2cji]], [[2j95|2j95]], [[2j38|2j38]], [[2boh|2boh]], [[2vvc|2vvc]], [[2w26|2w26]], [[1iqi|1iqi]], [[2vwm|2vwm]], [[1kye|1kye]], [[1iqk|1iqk]], [[1v3x|1v3x]], [[2fzz|2fzz]], [[2j2u|2j2u]], [[1iql|1iql]], [[1ksn|1ksn]], [[2wyj|2wyj]]</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=2wyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wyg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wyg RCSB], [http://www.ebi.ac.uk/pdbsum/2wyg 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> | |||
== 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa inhibitors, incorporating neutral and basic monoaryl P4 groups, ultimately producing potent inhibitors with effective levels of anticoagulant activity and extended oral pharmacokinetic profiles. However, time dependant inhibition of Cytochrome P450 3A4 was a particular issue with this series. | |||
Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with monoaryl P4 motifs.,Kleanthous S, Borthwick AD, Brown D, Burns-Kurtis CL, Campbell M, Chaudry L, Chan C, Clarte MO, Convery MA, Harling JD, Hortense E, Irving WR, Irvine S, Pateman AJ, Patikis AN, Pinto IL, Pollard DR, Roethka TJ, Senger S, Shah GP, Stelman GJ, Toomey JR, Watson NS, West RI, Whittaker C, Zhou P, Young RJ Bioorg Med Chem Lett. 2010 Jan 15;20(2):618-22. Epub 2009 Nov 20. PMID:20006499<ref>PMID:20006499</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Factor Xa|Factor Xa]] | *[[Factor Xa|Factor Xa]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Coagulation factor Xa]] | [[Category: Coagulation factor Xa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Borthwick, A D | [[Category: Borthwick, A D]] | ||
[[Category: Brown, D | [[Category: Brown, D]] | ||
[[Category: Burns-Kurtis, C L | [[Category: Burns-Kurtis, C L]] | ||
[[Category: Campbell, M | [[Category: Campbell, M]] | ||
[[Category: Chan, C | [[Category: Chan, C]] | ||
[[Category: Chaudry, L | [[Category: Chaudry, L]] | ||
[[Category: Clarte, M | [[Category: Clarte, M]] | ||
[[Category: Convery, M A | [[Category: Convery, M A]] | ||
[[Category: Harling, J D | [[Category: Harling, J D]] | ||
[[Category: Hortense, E | [[Category: Hortense, E]] | ||
[[Category: Irvine, S | [[Category: Irvine, S]] | ||
[[Category: Irving, W R | [[Category: Irving, W R]] | ||
[[Category: Kleanthous, S | [[Category: Kleanthous, S]] | ||
[[Category: Pateman, A J | [[Category: Pateman, A J]] | ||
[[Category: Patikis, A | [[Category: Patikis, A]] | ||
[[Category: Pinto, I L | [[Category: Pinto, I L]] | ||
[[Category: Pollard, D R | [[Category: Pollard, D R]] | ||
[[Category: Roethka, T J | [[Category: Roethka, T J]] | ||
[[Category: Senger, S | [[Category: Senger, S]] | ||
[[Category: Shah, G P | [[Category: Shah, G P]] | ||
[[Category: Stelman, G J | [[Category: Stelman, G J]] | ||
[[Category: Toomey, J R | [[Category: Toomey, J R]] | ||
[[Category: Watson, N S | [[Category: Watson, N S]] | ||
[[Category: Whittaker, C | [[Category: Whittaker, C]] | ||
[[Category: Young, R J | [[Category: Young, R J]] | ||
[[Category: Zhou, P | [[Category: Zhou, P]] | ||
[[Category: Blood clotting]] | [[Category: Blood clotting]] | ||
[[Category: Blood coagulation]] | [[Category: Blood coagulation]] | ||
