 |
PDBsum entry 3lc3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
3lc3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Studies of benzothiophene template as potent factor ixa (fixa) inhibitors in thrombosis.
|
|
|
Authors
|
|
S.Wang,
R.Beck,
T.Blench,
A.Burd,
S.Buxton,
M.Malic,
T.Ayele,
S.Shaikh,
S.Chahwala,
C.Chander,
R.Holland,
S.Merette,
L.Zhao,
M.Blackney,
A.Watts.
|
|
|
Ref.
|
|
J Med Chem, 2010,
53,
1465-1472.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
FIXa is a serine protease enzyme involved in the intrinsic pathway of the
coagulation cascade. The upstream intervention of the coagulation cascade in
selectively inhibiting FIXa would leave hemostasis intact via the extrinsic
pathway, leading to an optimum combination of efficacy and safety with low
incidence of bleeding. We have identified 2-amindinobenzothiophene template as a
lead scaffold for FIXa inhibiton based on its homology with urokinase
plasminogen activator (uPA). Subsequent SAR work on the template revealed a
number of highly potent FIXa inhibitors, though with moderate selectivity
against FXa. X-ray study with one of the analogues demonstrated active site
binding interaction with the induced opening of the S1 beta pocket and a
secondary binding at the S2-S4 sites, which is in direct contrast with the
previous finding.
|
|
|
|
|
|
|
