Design, synthesis and biological evaluation of new potent and highly selective ROS1-tyrosine kinase inhibitor

Title
Design, synthesis and biological evaluation of new potent and highly selective ROS1-tyrosine kinase inhibitor
Authors
박병선무스타파유경호오창현조승주한동근이희승이재열이소하
Keywords
ROS1; Astrocytoma; Glioblastoma multiforme; Pyrazole; Selectivity; Cancer; Kinase inhibitor; Tyrosine kinase
Issue Date
2009-08
Publisher
Bioorganic & medicinal chemistry letters
Citation
VOL 19, 4720-4723
Abstract
ROS1 protein is a receptor tyrosine kinase that has been reported mainly in meningiomas and astrocytomas, and until now, there is no selective inhibitor for this kinase. In this study, we illustrate for the synthesis of a highly potent and selective inhibitor for ROS1 kinase. The synthesized compound 1 was tested initially at a single dose concentration of 10 lM over 45 different kinases. At this concentration, a 94% inhibition of the enzymatic activity of ROS1 kinase was observed, while the inhibition in activity was below 30% in all of the other kinases. The pyrazole compound 1 was further tested in a 10-dose IC50 mode and showed an IC50 value of 199 nM for ROS1 kinase. The compound 1 can be used as a promising lead for the development of new selective inhibitors for ROS1 kinase, and it may open the way for new selective therapeutics for astrocytomas.
URI
http://pubs.kist.re.kr/handle/201004/35625
ISSN
0960-894X
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KIST Publication > Article
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