El-Deeb, Ibrahim M. Park, Byung Sun Jung, Su Jin Yoo, Kyung Ho Oh, Chang-Hyun Cho, Seung Joo Han, Dong Keun Lee, Jae Yeol Lee, So Ha 2024-01-20T20:32:21Z 2024-01-20T20:32:21Z 2021-09-01 2009-10-01 0960-894X https://pubs.kist.re.kr/handle/201004/132043 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. (C) 2009 Elsevier Ltd. All rights reserved. English Pergamon Press Ltd. C-ROS BIOLOGICAL EVALUATION GENE-MUTATIONS GLIOBLASTOMA CANCER EXPRESSION PATHWAYS POTENT Design, synthesis, screening, and molecular modeling study of a new series of ROS1 receptor tyrosine kinase inhibitors Article 10.1016/j.bmcl.2009.08.029 1 Bioorganic & Medicinal Chemistry Letters, v.19, no.19, pp.5622 - 5626 Bioorganic & Medicinal Chemistry Letters 19 19 5622 5626 scie scopus 000270106700022 2-s2.0-69949108857 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article C-ROS BIOLOGICAL EVALUATION GENE-MUTATIONS GLIOBLASTOMA CANCER EXPRESSION PATHWAYS POTENT Kinase inhibitors ROS1 Glioblastoma multiforme Homology modeling Pyrazole