Design, synthesis and biological evaluation of new potent and highly selective ROS1-tyrosine kinase inhibitor
- Design, synthesis and biological evaluation of new potent and highly selective ROS1-tyrosine kinase inhibitor
- 박병선; 무스타파; 유경호; 오창현; 조승주; 한동근; 이희승; 이재열; 이소하
- ROS1; Astrocytoma; Glioblastoma multiforme; Pyrazole; Selectivity; Cancer; Kinase inhibitor; Tyrosine kinase
- Issue Date
- Bioorganic & medicinal chemistry letters
- VOL 19, 4720-4723
- 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.
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