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

Cited 29 time in WEB OF SCIENCE Cited 31 time in Scopus
Title
Design, synthesis and biological evaluation of new potent and highly selective ROS1-tyrosine kinase inhibitor
Author(s)
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
KIOST Author(s)
Lee, Hyi Seung(이희승)
Publication Year
2009-08-15
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 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.
ISSN
0960-894X
URI
https://sciwatch.kiost.ac.kr/handle/2020.kiost/4267
DOI
10.1016/j.bmcl.2009.06.066
Bibliographic Citation
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v.19, no.16, pp.4720 - 4723, 2009
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Subject
TYROSINE KINASE; GLIOBLASTOMA-MULTIFORME; STAUROSPORINE ANALOGS; ROS; GENE; EXPRESSION; MUTATIONS; CANCER; CELLS
Keywords
ROS1; Tyrosine kinase; Kinase inhibitor; Astrocytoma; Glioblastoma multiforme; Pyrazole; Selectivity; Cancer
Type
Article
Language
English
Document Type
Article
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
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