 |
PDBsum entry 2g00
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Hydrolase
|
|
|
Title:
|
|
Factor xa in complex with the inhibitor 3-(6-(2'-((dimethylamino) methyl)-4-biphenylyl)-7-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro- 1h-pyrazolo[3,4-c]pyridin-1-yl)benzamide
|
|
Structure:
|
|
Coagulation factor x. Chain: a. Fragment: coagulation factor x, heavy chain. Synonym: stuart factor, stuart-prower factor. Other_details: proteolytic cleavage product. Coagulation factor x. Chain: l. Fragment: coagulation factor x, light chain. Synonym: stuart factor, stuart-prower factor.
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
|
|
Biol. unit:
|
|
Dimer (from
)
|
|
Resolution:
|
|
|
2.10Å
|
R-factor:
|
0.269
|
R-free:
|
0.284
|
|
|
Authors:
|
|
R.S.Alexander
|
|
Key ref:
|
|
D.J.Pinto
et al.
(2006).
Discovery of potent, efficacious, and orally bioavailable inhibitors of blood coagulation factor Xa with neutral P1 moieties.
Bioorg Med Chem Lett,
16,
5584-5589.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
10-Feb-06
|
Release date:
|
03-Oct-06
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
Chains A, L:
E.C.3.4.21.6
- coagulation factor Xa.
|
|
|
|
|
|
|
Reaction:
|
|
Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Bioorg Med Chem Lett
16:5584-5589
(2006)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Discovery of potent, efficacious, and orally bioavailable inhibitors of blood coagulation factor Xa with neutral P1 moieties.
|
|
D.J.Pinto,
R.A.Galemmo,
M.L.Quan,
M.J.Orwat,
C.Clark,
R.Li,
B.Wells,
F.Woerner,
R.S.Alexander,
K.A.Rossi,
A.Smallwood,
P.C.Wong,
J.M.Luettgen,
A.R.Rendina,
R.M.Knabb,
K.He,
R.R.Wexler,
P.Y.Lam.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The bicyclic dihydropyrazolopyridinone scaffold allowed for incorporation of
multiple P1 moieties with subnanomolar binding affinities for blood coagulation
factor Xa. The compound
3-[6-(2'-dimethylaminomethyl-biphenyl-4-yl)-7-oxo-3-trifluoro-methyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridine-l-yl]-benzamide
6d shows good fXa potency, selectivity, in vivo efficacy and oral
bioavailability. Compound 6d was selected for further pre-clinical evaluations.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
Y.K.Lee,
and
M.R.Player
(2011).
Developments in factor Xa inhibitors for the treatment of thromboembolic disorders.
|
| |
Med Res Rev,
31,
202-283.
|
|
|
|
|
|
|
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.
|
| |
J Am Chem Soc,
130,
2817-2831.
|
|
|
|
|
|
|
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.
|
| |
Chem Biol Drug Des,
70,
100-112.
|
|
|
PDB code:
|
|
|
|
|
|
|
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.
|
|
|
Links
