2pr3: Difference between revisions
New page: left|200px<br /> <applet load="2pr3" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pr3, resolution 1.5Å" /> '''Factor XA inhibitor'... |
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[[Image:2pr3. | [[Image:2pr3.jpg|left|200px]]<br /><applet load="2pr3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''Factor XA inhibitor'''<br /> | '''Factor XA inhibitor'''<br /> | ||
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==Overview== | ==Overview== | ||
A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor, Xa inhibitors using structure-based drug design. This series consisted of, a neutral 4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline, scaffold (1, IC(50) = 18 nM). Optimization of the initial hit resulted in, an orally bioavailable, subnanomolar inhibitor of factor Xa (13, IC(50) =, 0.38 nM), which was shown to be efficacious in a canine electrolytic model, of thrombosis with minimal bleeding. | A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor, Xa inhibitors using structure-based drug design. This series consisted of, a neutral 4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline, scaffold (1, IC(50) = 18 nM). Optimization of the initial hit resulted in, an orally bioavailable, subnanomolar inhibitor of factor Xa (13, IC(50) =, 0.38 nM), which was shown to be efficacious in a canine electrolytic model, of thrombosis with minimal bleeding. | ||
==About this Structure== | ==About this Structure== | ||
2PR3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and 237 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 2PR3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=237:'>237</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PR3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: fxa coagulation factor inhibitor]] | [[Category: fxa coagulation factor inhibitor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:37:29 2008'' | ||
Revision as of 14:37, 23 January 2008
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Factor XA inhibitor
OverviewOverview
A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor, Xa inhibitors using structure-based drug design. This series consisted of, a neutral 4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline, scaffold (1, IC(50) = 18 nM). Optimization of the initial hit resulted in, an orally bioavailable, subnanomolar inhibitor of factor Xa (13, IC(50) =, 0.38 nM), which was shown to be efficacious in a canine electrolytic model, of thrombosis with minimal bleeding.
About this StructureAbout this Structure
2PR3 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Coagulation factor Xa, with EC number 3.4.21.6 Full crystallographic information is available from OCA.
ReferenceReference
Structure-based drug design of pyrrolidine-1, 2-dicarboxamides as a novel series of orally bioavailable factor Xa inhibitors., Van Huis CA, Bigge CF, Casimiro-Garcia A, Cody WL, Dudley DA, Filipski KJ, Heemstra RJ, Kohrt JT, Narasimhan LS, Schaum RP, Zhang E, Bryant JW, Haarer S, Janiczek N, Leadley RJ Jr, McClanahan T, Thomas Peterson J, Welch KM, Edmunds JJ, Chem Biol Drug Des. 2007 Jun;69(6):444-50. PMID:17581239
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