A novel imidazopyridine analogue as a phosphatidylinositol 3-kinase inhibitor against human breast cancer

Cancer Lett. 2012 May 1;318(1):68-75. doi: 10.1016/j.canlet.2011.12.001. Epub 2011 Dec 8.

Abstract

Potentiation of anti-breast cancer activity of an imidazopyridine-based PI3Kα inhibitor, HS-104, was investigated in human breast cancer cells. HS-104 shows strong inhibitory activity against recombinant PI3Kα isoform and the PI3K signaling pathway, resulting in anti-proliferative activity in breast cancer cells. It also induced cell cycle arrest at the G(2)/M phase as well as apoptosis. Furthermore, oral administration of HS-104 significantly inhibited the growth of tumor in SkBr3 mouse xenograft models. Therefore, HS-104 could be considered as a potential candidate for the treatment of human breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Imidazoles / pharmacology*
  • Immunoenzyme Techniques
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Pyridines / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Enzyme Inhibitors
  • HS-104
  • Imidazoles
  • Phosphoinositide-3 Kinase Inhibitors
  • Pyridines
  • Phosphatidylinositol 3-Kinase