2pr3
From Proteopedia
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| , resolution 1.5Å | |||||||
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| Ligands: | , | ||||||
| Gene: | F10 (Homo sapiens) | ||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||
| Related: | 2G0M, 2G21, 2PHB
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Factor XA inhibitor
Contents |
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.
Disease
Known disease associated with this structure: Factor X deficiency OMIM:[227600]
About this Structure
2PR3 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Mon Mar 31 04:39:36 2008
