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PDBsum entry 2pr3
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Blood clotting
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PDB id
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2pr3
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Contents |
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* Residue conservation analysis
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PDB id:
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Blood clotting
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Title:
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Factor xa inhibitor
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Structure:
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Coagulation factor x, heavy chain. Chain: a. Fragment: heavy chain. Synonym: stuart factor, heavy chain. Stuart-prower factor, heavy chain. Activated factor xa heavy chain. Engineered: yes. Coagulation factor x, light chain. Chain: b. Fragment: light chain.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: f10. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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1.50Å
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R-factor:
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0.255
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R-free:
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0.267
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Authors:
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E.Zhang,J.T.Kohrt,C.F.Bigge,B.C.Finzel
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Key ref:
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C.A.Van Huis
et al.
(2007).
Structure-based drug design of pyrrolidine-1, 2-dicarboxamides as a novel series of orally bioavailable factor Xa inhibitors.
Chem Biol Drug Des,
69,
444-450.
PubMed id:
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Date:
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03-May-07
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Release date:
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14-Aug-07
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PROCHECK
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Headers
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References
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Enzyme class:
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Chains A, B:
E.C.3.4.21.6
- coagulation factor Xa.
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Reaction:
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Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.
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Chem Biol Drug Des
69:444-450
(2007)
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PubMed id:
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Structure-based drug design of pyrrolidine-1, 2-dicarboxamides as a novel series of orally bioavailable factor Xa inhibitors.
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C.A.Van Huis,
C.F.Bigge,
A.Casimiro-Garcia,
W.L.Cody,
D.A.Dudley,
K.J.Filipski,
R.J.Heemstra,
J.T.Kohrt,
L.S.Narasimhan,
R.P.Schaum,
E.Zhang,
J.W.Bryant,
S.Haarer,
N.Janiczek,
R.J.Leadley,
T.McClanahan,
J.Thomas Peterson,
K.M.Welch,
J.J.Edmunds.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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Y.K.Lee,
and
M.R.Player
(2011).
Developments in factor Xa inhibitors for the treatment of thromboembolic disorders.
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Med Res Rev,
31,
202-283.
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J.T.Kohrt,
C.F.Bigge,
J.W.Bryant,
A.Casimiro-Garcia,
L.Chi,
W.L.Cody,
T.Dahring,
D.A.Dudley,
K.J.Filipski,
S.Haarer,
R.Heemstra,
N.Janiczek,
L.Narasimhan,
T.McClanahan,
J.T.Peterson,
V.Sahasrabudhe,
R.Schaum,
C.A.Van Huis,
K.M.Welch,
E.Zhang,
R.J.Leadley,
and
J.J.Edmunds
(2007).
The discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarboxamide (PD 0348292), an orally efficacious factor Xa inhibitor.
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Chem Biol Drug Des,
70,
100-112.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
