5qtt

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Current revision (07:27, 17 October 2024) (edit) (undo)
 
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<table><tr><td colspan='2'>[[5qtt]] is a 1 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=5QTT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QTT FirstGlance]. <br>
<table><tr><td colspan='2'>[[5qtt]] is a 1 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=5QTT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QTT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.23&#8491;</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]] 2.23&#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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QEY:methyl+[(3R,7S)-7-{[5-amino-1-(3-chloro-2-fluorophenyl)-1H-pyrazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate'>QEY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QEY:methyl+~{N}-[(10~{R},14~{S})-14-[[5-azanyl-1-(3-chloranyl-2-fluoranyl-phenyl)pyrazol-4-yl]carbonylamino]-10-methyl-9-oxidanylidene-8,16-diazatricyclo[13.3.1.0^{2,7}]nonadeca-1(18),2,4,6,15(19),16-hexaen-5-yl]carbamate'>QEY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5qtt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtt OCA], [https://pdbe.org/5qtt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qtt RCSB], [https://www.ebi.ac.uk/pdbsum/5qtt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtt 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=5qtt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtt OCA], [https://pdbe.org/5qtt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qtt RCSB], [https://www.ebi.ac.uk/pdbsum/5qtt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtt ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
== Function ==
[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.
[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Factor XIa inhibitors are promising novel anticoagulants which show excellent efficacy in preclinical thrombosis models with minimal effects on hemostasis. The discovery of potent and selective FXIa inhibitors which are also orally bioavailable has been a challenge. Here, we describe optimization of the imidazole-based macrocyclic series and our initial progress towards meeting this challenge. A two-pronged strategy, which focused on replacement of the imidazole scaffold and the design of new P1 groups, led to the discovery of potent, orally bioavailable pyridine-based macrocyclic FXIa inhibitors. Moreover, pyridine-based macrocycle 19, possessing the phenylimidazole carboxamide P1, exhibited excellent selectivity against relevant blood coagulation enzymes and displayed antithrombotic efficacy in a rabbit thrombosis model.
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Potent, Orally Bioavailable and Efficacious Macrocyclic Inhibitors of Factor XIa. Discovery of Pyridine-Based Macrocycles Possessing Phenylazole Carboxamide P1 Groups.,Corte JR, Pinto DJP, Fang T, Osuna H, Yang W, Wang Y, Lai A, Clark C, Sun JH, Rampulla RA, Mathur A, Kaspady M, Neithnadka PR, Li YX, Rossi KA, Myers JE, Sheriff S, Lou Z, Harper TW, Huang CS, Zheng JJ, Bozarth JM, Wu Y, Wong PC, Crain E, Seiffert DA, Luettgen JM, Lam P, Wexler RR, Ewing WR J Med Chem. 2019 Dec 13. doi: 10.1021/acs.jmedchem.9b01768. PMID:31833761<ref>PMID:31833761</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 5qtt" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==

Current revision

FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl [(3R,7S)-7-{[5-amino-1-(3-chloro-2-fluorophenyl)-1H-pyrazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate

PDB ID 5qtt

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