 |
PDBsum entry 4jz1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
4jz1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Discovery of pyridyl bis(oxy)dibenzimidamide derivatives as selective matriptase inhibitors.
|
|
|
Authors
|
|
R.Goswami,
S.Mukherjee,
G.Wohlfahrt,
C.Ghadiyaram,
J.Nagaraj,
B.R.Chandra,
R.K.Sistla,
L.K.Satyam,
D.S.Samiulla,
A.Moilanen,
H.S.Subramanya,
M.Ramachandra.
|
|
|
Ref.
|
|
Acs Med Chem Lett, 2013,
4,
1152-1157.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Matriptase belongs to trypsin-like serine proteases involved in matrix
remodeling/degradation, growth regulation, survival, motility, and cell
morphogenesis. Herein, we report a structure-based approach, which led to the
discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as
potent and selective matriptase inhibitors. Co-crystal structures of selected
compounds in complex with matriptase supported compound designing. Additionally,
WaterMap analyses indicated the possibility of occupying a distinct pocket
within the catalytic domain, exploration of which resulted in >100-fold
improvement in potency. Co-crystal structure of 10 with matriptase revealed
critical interactions leading to potent target inhibition and selectivity
against other serine proteases.
|
|
|
|
|
|
|
