Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer

Cancer Lett. 2011 Mar 28;302(2):155-65. doi: 10.1016/j.canlet.2011.01.010.


Trastuzumab, a HER2 directed treatment has shown clinical benefit in HER2 amplified gastric cancer. This study demonstrated the potent antitumor activity of HM781-36B, a quinazoline-based irreversible pan-HER inhibitor, in HER2 amplified gastric cancer cells (SNU216 and N87) in vitro and in vivo. HM781-36B inhibited phosphorylation of HER family and downstream signaling molecules, and induced apoptosis and G1 arrest. Furthermore, HM781-36B exerted synergistic effects with chemotherapeutic agents in both HER2 amplified and HER2 non-amplified gastric cancer cells. Therefore, HM781-36B may be useful for the treatment of HER2 amplified gastric cancer alone or in combination with chemotherapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Synergism
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Phosphorylation / drug effects
  • Quinazolines / pharmacology
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Stomach Neoplasms / drug therapy


  • Antineoplastic Agents
  • HM781-36B
  • Quinazolines
  • ErbB Receptors
  • Receptor, ErbB-2
  • Cisplatin