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PDBsum entry 2phb
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Blood clotting
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PDB id
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2phb
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Blood clotting
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Title:
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An orally efficacious 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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2.30Å
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R-factor:
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0.260
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R-free:
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0.296
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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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J.T.Kohrt
et al.
(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.
Chem Biol Drug Des,
70,
100-112.
PubMed id:
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Date:
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10-Apr-07
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Release date:
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25-Mar-08
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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
70:100-112
(2007)
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PubMed id:
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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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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,
J.J.Edmunds.
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ABSTRACT
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Herein, we report the discovery of novel, proline-based factor Xa inhibitors
containing a neutral P1 chlorophenyl pharmacophore. Through the additional
incorporation of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one 22, as a P4
pharmacophore, we discovered compound 7 (PD 0348292). This compound is a
selective, orally bioavailable, efficacious FXa inhibitor that is currently in
phase II clinical trials for the treatment and prevention of thrombotic
disorders.
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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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E.Perzborn,
S.Roehrig,
A.Straub,
D.Kubitza,
and
F.Misselwitz
(2011).
The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor.
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Nat Rev Drug Discov,
10,
61-75.
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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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H.J.Rupprecht,
and
R.Blank
(2010).
Clinical pharmacology of direct and indirect factor Xa inhibitors.
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Drugs,
70,
2153-2170.
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R.S.Mehta
(2010).
Novel oral anticoagulants for prophylaxis and treatment of venous thromboembolism: part I (Factor Xa inhibitors).
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Expert Rev Hematol,
3,
227-241.
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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.
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Links
