EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance

Cancer Lett. 2017 Jan 28:385:51-54. doi: 10.1016/j.canlet.2016.11.008. Epub 2016 Nov 10.

Abstract

The third-generation tyrosine kinase inhibitors (TKI), AZD9291 (osimertinib) and CO-1686 (rociletinib) of epidermal growth factor receptor (EGFR) are highly active against T790M positive non-small cell lung cancer (NSCLC). However, resistance develops rapidly. EGFR C797S mutation was reported to be a leading mechanism of resistance to the third-generation inhibitors. The C797S mutation appears to be an ideal target for overcoming the acquired resistance to the third-generation inhibitors. This review summarizes the latest development on the discovery of a fourth-generation EGFR TKI, EAI045.3.

Keywords: AZD9291; EAI045; EGFR; NSCLC; Rociletinib; TKI; epidermal growth factor receptor; non-small cell lung cancer; tyrosine kinase inhibitor.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Benzeneacetamides / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Design*
  • Drug Resistance, Neoplasm* / genetics
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Molecular Targeted Therapy
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects
  • Thiazoles / therapeutic use*

Substances

  • Antineoplastic Agents
  • Benzeneacetamides
  • EAI045
  • Protein Kinase Inhibitors
  • Thiazoles
  • EGFR protein, human
  • ErbB Receptors