Park, Byung Sun El-Deeb, Ibrahim M. Yoo, Kyung Ho Oh, Chang-Hyun Cho, Seung Joo Han, Dong Keun Lee, Hye-Seung Lee, Jae Yeol Lee, So Ha 2024-01-20T21:01:30Z 2024-01-20T21:01:30Z 2021-09-03 2009-08-15 0960-894X https://pubs.kist.re.kr/handle/201004/132233 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. English Pergamon Press Ltd. TYROSINE KINASE GLIOBLASTOMA-MULTIFORME STAUROSPORINE ANALOGS ROS GENE EXPRESSION MUTATIONS CANCER CELLS Design, synthesis and biological evaluation of new potent and highly selective ROS1-tyrosine kinase inhibitor Article 10.1016/j.bmcl.2009.06.066 1 Bioorganic & Medicinal Chemistry Letters, v.19, no.16, pp.4720 - 4723 Bioorganic & Medicinal Chemistry Letters 19 16 4720 4723 scie scopus 000268358800041 2-s2.0-67651091687 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article TYROSINE KINASE GLIOBLASTOMA-MULTIFORME STAUROSPORINE ANALOGS ROS GENE EXPRESSION MUTATIONS CANCER CELLS ROS1 Tyrosine kinase Kinase inhibitor Astrocytoma Glioblastoma multiforme Pyrazole Selectivity Cancer