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* Residue conservation analysis
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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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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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1 term
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Biological process
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proteolysis
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1 term
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Biochemical function
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catalytic activity
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3 terms
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DOI no:
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Bioorg Med Chem Lett
12:1671-1674
(2002)
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PubMed id:
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Optimization of the beta-aminoester class of factor Xa inhibitors. Part 2: Identification of FXV673 as a potent and selective inhibitor with excellent In vivo anticoagulant activity.
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K.R.Guertin,
C.J.Gardner,
S.I.Klein,
A.L.Zulli,
M.Czekaj,
Y.Gong,
A.P.Spada,
D.L.Cheney,
S.Maignan,
J.P.Guilloteau,
K.D.Brown,
D.J.Colussi,
V.Chu,
C.L.Heran,
S.R.Morgan,
R.G.Bentley,
C.T.Dunwiddie,
R.J.Leadley,
H.W.Pauls.
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ABSTRACT
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Further optimization of the beta-aminoester class of factor Xa (fXa) inhibitors
is described culminating in the identification of 9c (FXV673), a potent and
selective factor Xa inhibitor with excellent in vivo anticoagulant activity. An
X-ray structure of FXV673 bound to human fXa is also presented. Based on its
selectivity, potent in vivo activity and favorable pre-clinical safety profile,
FXV673 was selected for further development and is currently undergoing clinical
trials.
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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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Y.Tanrikulu,
E.Proschak,
T.Werner,
T.Geppert,
N.Todoroff,
A.Klenner,
T.Kottke,
K.Sander,
E.Schneider,
R.Seifert,
H.Stark,
T.Clark,
and
G.Schneider
(2009).
Homology model adjustment and ligand screening with a pseudoreceptor of the human histamine H4 receptor.
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ChemMedChem, 4,
820-827.
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E.Proschak,
M.Rupp,
S.Derksen,
and
G.Schneider
(2008).
Shapelets: possibilities and limitations of shape-based virtual screening.
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J Comput Chem, 29,
108-114.
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L.R.Liou,
A.J.McNeil,
G.E.Toombes,
and
D.B.Collum
(2008).
Structures of beta-amino ester enolates: new strategies using the method of continuous variation.
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J Am Chem Soc, 130,
17334-17341.
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N.Singh,
and
J.M.Briggs
(2008).
Molecular dynamics simulations of Factor Xa: insight into conformational transition of its binding subsites.
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Biopolymers, 89,
1104-1113.
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R.Abel,
T.Young,
R.Farid,
B.J.Berne,
and
R.A.Friesner
(2008).
Role of the active-site solvent in the thermodynamics of factor Xa ligand binding.
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J Am Chem Soc, 130,
2817-2831.
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S.Komoriya,
N.Haginoya,
S.Kobayashi,
T.Nagata,
A.Mochizuki,
M.Suzuki,
T.Yoshino,
H.Horino,
T.Nagahara,
M.Suzuki,
Y.Isobe,
and
T.Furugoori
(2005).
Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites.
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Bioorg Med Chem, 13,
3927-3954.
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PDB codes:
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J.Ruef,
and
H.A.Katus
(2003).
New antithrombotic drugs on the horizon.
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Expert Opin Investig Drugs, 12,
781-797.
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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
codes are
shown on the right.
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Links
