 |
PDBsum entry 4z55
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase/transferase inhibitor
|
PDB id
|
|
|
|
4z55
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Design and synthesis of novel selective anaplastic lymphoma kinase inhibitors.
|
|
|
Authors
|
|
P.Y.Michellys,
B.Chen,
T.Jiang,
Y.Jin,
W.Lu,
T.H.Marsilje,
W.Pei,
T.Uno,
X.Zhu,
B.Wu,
T.N.Nguyen,
B.Bursulaya,
C.Lee,
N.Li,
S.Kim,
T.Tuntland,
B.Liu,
F.Sun,
A.Steffy,
T.Hood.
|
|
|
Ref.
|
|
Bioorg Med Chem Lett, 2016,
26,
1090-1096.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase belonging to the
insulin receptor superfamily. Expression of ALK in normal human tissues is only
found in a subset of neural cells, however it is involved in the genesis of
several cancers through genetic aberrations involving translocation of the
kinase domain with multiple fusion partners (e.g., NPM-ALK in anaplastic large
cell lymphoma ALCL or EML4-ALK in non-small cell lung cancer) or activating
mutations in the full-length receptor resulting in ligand-independent
constitutive activation (e.g., neuroblastoma). Here we are reporting the
discovery of novel and selective anaplastic lymphoma kinase inhibitors from
specific modifications of the 2,4-diaminopyridine core present in TAE684 and
LDK378. Synthesis, structure activity relationships (SAR), absorption,
distribution, metabolism, and excretion (ADME) profile, and in vivo efficacy in
a mouse xenograft model of anaplastic large cell lymphoma are described.
|
|
|
|
|
|
|
