Ridaifen B, a tamoxifen derivative, directly binds to Grb10 interacting GYF protein 2

Bioorg Med Chem. 2013 Jan 1;21(1):311-20. doi: 10.1016/j.bmc.2012.10.037. Epub 2012 Oct 29.

Abstract

Ridaifen B (RID-B) is a tamoxifen derivative that potently inhibits breast tumor growth. RID-B was reported to show anti-proliferating activity for a variety of estrogen receptor (ER)-positive human cancer cells. Interestingly, RID-B was also reported to possess higher potency than that of tamoxifen even for some ER-negative cells, suggesting an ER-independent mechanism of action. In this study, a T7 phage display screen and subsequent binding analyses have identified Grb10 interacting GYF protein 2 (GIGYF2) as a RID-B-binding protein. Using a cell-based assay, the Akt phosphorylation level mediated by GIGYF2 was found to have decreased in the presence of RID-B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / pharmacology*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Surface Display Techniques
  • Humans
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrrolidines / pharmacology*
  • Signal Transduction / drug effects
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology

Substances

  • Antineoplastic Agents
  • Carrier Proteins
  • GIGYF2 protein, human
  • Pyrrolidines
  • ridaifen-B
  • Tamoxifen
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt