Evolution strategy of ROS1 kinase inhibitors for use in cancer therapy. (2nd July 2018)

• Record Type: Journal Article
• Authors: Liu, Siming; Yang, Haikui; Jiang, Ying; Zhang, Tingting; Yan, Ruohong; Zhang, Jiajie
• Is Part Of: Future medicinal chemistry. Volume 10:Number 14(2018)
• Page Start: 1705
• Page End: 1720
• Publication Date: 2018-07-02
• Subjects: computer-assisted technology -- hit-to-drug evolution -- NSCLC -- ROS1 inhibitor -- scaffold; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc-2018-0033
• Languages: English
• ISSNs: 1756-8919

Abstract

The abnormal expression of c-ros oncogene1 receptor tyrosine kinase (ROS1) has been identified as clinically actionable oncogenic driver in non-small-cell lung cancer. Since crizotinib was approved by the US FDA for the treatment of advanced ROS1-positive non-small-cell lung cancer, ROS1 kinase has become a promising therapeutic target. Under the guidance of some advanced computer-assisted technologies, such as structure-based drug design, homology modeling and lipophilic efficiency parameters, several potent and selective inhibitors against wild-type and mutant ROS1 were designed and synthesized. In this article, we will review a series of scaffolds targeting ROS1 kinase from the hit-to-drug evolution strategies of their representative compounds and it is hoped that these design strategies would facilitate medicinal chemists to optimize the process of drug design.