2pr3: Difference between revisions
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==Overview== | ==Overview== | ||
A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor | 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. | ||
==Disease== | |||
Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Bigge, C | [[Category: Bigge, C F.]] | ||
[[Category: Finzel, B | [[Category: Finzel, B C.]] | ||
[[Category: Kohrt, J | [[Category: Kohrt, J T.]] | ||
[[Category: Zhang, E.]] | [[Category: Zhang, E.]] | ||
[[Category: 237]] | [[Category: 237]] | ||
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[[Category: fxa coagulation factor inhibitor]] | [[Category: fxa coagulation factor inhibitor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:32:12 2008'' | ||
Revision as of 19:32, 21 February 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.
DiseaseDisease
Known disease associated with this structure: Factor X deficiency OMIM:[227600]
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
Page seeded by OCA on Thu Feb 21 18:32:12 2008