ROS1 kinase inhibitors for molecular-targeted therapies

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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
Volume23
Issue number2
Publication statusPublished - 2016 Jan 1

Fingerprint

Molecular Targeted Therapy
Phosphotransferases
Neoplasms
Hemangiosarcoma
Pharmaceutical Chemistry
Receptor Protein-Tyrosine Kinases
Drug Discovery
Glioblastoma
Sequence Homology
Non-Small Cell Lung Carcinoma
Ovarian Neoplasms
Stomach Neoplasms
Cell Movement
Colorectal Neoplasms
Lung Neoplasms
Adenocarcinoma
Apoptosis
Survival
Proteins

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Al-Sanea, M. M., Abdelazem, A. Z., Park, B. S., Yoo, K. H., Sim, T., Kwon, Y. J., & Lee, S. H. (2016). ROS1 kinase inhibitors for molecular-targeted therapies. Current Medicinal Chemistry, 23(2), 142-160.

ROS1 kinase inhibitors for molecular-targeted therapies. / Al-Sanea, M. M.; Abdelazem, A. Z.; Park, B. S.; Yoo, K. H.; Sim, Taebo; Kwon, Y. J.; Lee, S. H.

In: Current Medicinal Chemistry, Vol. 23, No. 2, 01.01.2016, p. 142-160.

Research output: Contribution to journalArticle

Al-Sanea, MM, Abdelazem, AZ, Park, BS, Yoo, KH, Sim, T, Kwon, YJ & Lee, SH 2016, 'ROS1 kinase inhibitors for molecular-targeted therapies', Current Medicinal Chemistry, vol. 23, no. 2, pp. 142-160.
Al-Sanea MM, Abdelazem AZ, Park BS, Yoo KH, Sim T, Kwon YJ et al. ROS1 kinase inhibitors for molecular-targeted therapies. Current Medicinal Chemistry. 2016 Jan 1;23(2):142-160.
Al-Sanea, M. M. ; Abdelazem, A. Z. ; Park, B. S. ; Yoo, K. H. ; Sim, Taebo ; Kwon, Y. J. ; Lee, S. H. / ROS1 kinase inhibitors for molecular-targeted therapies. In: Current Medicinal Chemistry. 2016 ; Vol. 23, No. 2. pp. 142-160.
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