 |
PDBsum entry 3hv3
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Displacement assay for the detection of stabilizers of inactive kinase conformations.
|
|
|
Authors
|
|
S.Klüter,
C.Grütter,
T.Naqvi,
M.Rabiller,
J.R.Simard,
V.Pawar,
M.Getlik,
D.Rauh.
|
|
|
Ref.
|
|
J Med Chem, 2010,
53,
357-367.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Targeting protein kinases with small molecules outside the highly conserved ATP
pocket to stabilize inactive kinase conformations is becoming a more desirable
approach in kinase inhibitor research, since these molecules have advanced
pharmacological properties compared to compounds exclusively targeting the ATP
pocket. Traditional screening approaches for kinase inhibitors are often based
on enzyme activity, but they may miss inhibitors that stabilize inactive kinase
conformations by enriching the active state of the kinase. Here we present the
development of a kinase binding assay employing a pyrazolourea type III
inhibitor and enzyme fragment complementation (EFC) technology that is suitable
to screen stabilizers of enzymatically inactive kinases. To validate this assay
system, we report the binding characteristics of a series of kinase inhibitors
to inactive p38alpha and JNK2. Additionally, we present protein X-ray
crystallography studies to examine the binding modes of potent quinoline-based
DFG-out binders in p38alpha.
|
|
|
|
|
|
|
