Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 19, Issue 16, Pages 4720-4723Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.06.066
Keywords
ROS1; Tyrosine kinase; Kinase inhibitor; Astrocytoma; Glioblastoma multiforme; Pyrazole; Selectivity; Cancer
Categories
Funding
- Korea Institute of Science and Technology
- Ministry of Education, Science and Technology [M10711060001-08M1106-00110]
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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 mu M 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. (C) 2009 Elsevier Ltd. All rights reserved.
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