Small-Molecule Inhibitors of the c-Fes Protein-Tyrosine Kinase

Title
Small-Molecule Inhibitors of the c-Fes Protein-Tyrosine Kinase
Authors
Sabine HellwigChandra V. MiduturuShigeru KandaJianming ZhangPanagis FilippakopoulosEidarus SalahXianming DengHwan Geun ChoiWenjun Zhou허우영Stefan KnappNathanael S. GrayThomas E. Smithgall
Issue Date
2012-04
Publisher
Chemistry & biology
Citation
VOL 19, 529-540
Abstract
The c-Fes protein-tyrosine kinase modulates cellular signaling pathways governing differentiation, the innate immune response, and vasculogenesis. Here, we report the identification of types I and II kinase inhibitors with potent activity against c-Fes both in vitro and in cell-based assays. One of the most potent inhibitors is the previously described anaplastic lymphoma kinase inhibitor TAE684. The crystal structure of TAE684 in complex with the c-Fes SH2-kinase domain showed excellent shape complementarity with the ATP-binding pocket and a key role for the gatekeeper methionine in the inhibitory mechanism. TAE684 and two pyrazolopyrimidines with nanomolar potency against c-Fes in vitro were used to establish a role for this kinase in osteoclastogenesis, illustrating the value of these inhibitors as tool compounds to probe the diverse biological functions associated with this unique kinase.
URI
http://pubs.kist.re.kr/handle/201004/49736
ISSN
10745521
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE