Design, Synthesis, Screening and Molecular Modeling Study of a New Series of Ros1 Receptor Tyrosine Kinase Inhibitors

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Title Design, Synthesis, Screening and Molecular Modeling Study of a New Series of Ros1 Receptor Tyrosine Kinase Inhibitors
Author El-Deeb, Ibrahim Mustafa; Park, Byung Sun; Jung, Su Jin; Yoo, Kyung Ho; Oh, Chang-Hyun; Cho, Seung Joo; Han, Dong Keun; Lee, Jae Yeol; Lee, So Ha
Journal Name Bioorganic & Medicinal Chemistry Letters
Year Published 2009
Place of publication United Kingdom
Publisher Elsevier
Abstract A series of rationally designed ROS1 tyrosine kinase inhibitors was synthesized and screened. Compound 12b has showed good potency with IC50 value of 209 nM, which is comparable with that of the reference lead compound 1. Molecular modeling studies have been performed, that is, a homology model for ROS1 was built, and the screened inhibitors were docked into its major identified binding site. The docked poses along with the activity data have revealed a group of the essential features for activity. Overall, simplification of the lead compound 1 into compound 12b has maintained the activity, while facilitated the synthetic advantages. A molecular interaction model for ROS1 kinase and inhibitors has been proposed.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/j.bmcl.2009.08.029
Copyright Statement Copyright 2009 Elsevier. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
Volume 19
Issue Number 19
Page from 5622
Page to 5626
ISSN 0960-894X
Date Accessioned 2011-03-18
Date Available 2011-10-21T07:24:53Z
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Biologically Active Molecules
URI http://hdl.handle.net/10072/37924
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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