HS-173, a novel phosphatidylinositol 3-kinase (PI3K) inhibitor, has anti-tumor activity through promoting apoptosis and inhibiting angiogenesis

Cancer Lett. 2013 Jan 1;328(1):152-9. doi: 10.1016/j.canlet.2012.08.020. Epub 2012 Aug 26.

Abstract

We synthesized a novel imidazopyridine analogue, a PI3Kα inhibitor HS-173 and investigated anti-cancer capacity in human cancer cells. HS-173 inhibited the PI3K signaling pathway, and showed anti-proliferative effects on cancer cells. Also, HS-173 induced cell cycle arrest at the G(2)/M phase and apoptosis. In addition, HS-173 decreased the expression HIF-1α and VEGF which play an important role in angiogenesis. This effect was confirmed by the suppression of tube formation and migration assay in vitro. Furthermore, HS-173 diminished blood vessel formation in the Matrigel plug assay in mice. Therefore, HS-173 is considered as a novel drug candidate to treat cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neovascularization, Pathologic / enzymology*
  • Phosphoinositide-3 Kinase Inhibitors*
  • Pyridines / pharmacology*
  • Sulfonamides / pharmacology*

Substances

  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Pyridines
  • Sulfonamides
  • ethyl 6-(5-(phenylsulfonamido)pyridin-3-yl)imidazo(1,2-a)pyridine-3-carboxylate