ROS1 kinase inhibitors for molecular-targeted therapies

M. M. Al-Sanea, A. Z. Abdelazem, B. S. Park, K. H. Yoo, T. Sim, Y. J. Kwon, S. H. Lee

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


ROS1 is a pivotal transmembrane receptor protein tyrosine kinase which regulates several cellular processes like apoptosis, survival, differentiation, proliferation, cell migration, and transformation. There is increasing evidence supporting that ROS1 plays an important role in different malignancies including glioblastoma, colorectal cancer, gastric adenocarcinoma, inflammatory myofibroblastic tumor, ovarian cancer, angiosarcoma, and non small cell lung cancer; thus, ROS1 has become a potential drug discovery target. ROS1 shares about 49% sequence homology with ALK primary structure; therefore, wide range of ALK kinase inhibitors have shown in vitro inhibitory activity against ROS1 kinase. After Crizotinib approval by FDA for the management of ALK-rearranged lung cancer, ROS1-positive tumors have been focused. Although significant advancements have been achieved in understanding ROS1 function and its signaling pathways plus recent discovery of small molecules modulating ROS1 protein, a vital need of medicinal chemistry efforts is still required to produce selective and potent ROS1 inhibitors as an important therapeutic strategy for different human malignancies. This review focuses on the current knowledge about different scaffolds targeting ROS1 rearrangements, methods to synthesis, and some biological data about the most potent compounds that have delivered various scaffold structures.

Original languageEnglish
Pages (from-to)142-160
Number of pages19
JournalCurrent Medicinal Chemistry
Issue number2
Publication statusPublished - 2016 Jan 1


  • Cancer
  • Inhibitor
  • ROS1 kinase
  • Receptor tyrosine kinase
  • Translocation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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