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

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.

• Authors: Senko Tsukuda, Tomoe Kusayanagi, Eri Umeda, Chihiro Watanabe, Yu-ta Tosaki, Shinji Kamisuki, Toshifumi Takeuchi, Yoichi Takakusagi, Isamu Shiina, Fumio Sugawara
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 21 Issue 1 Pg. 311-20 (Jan 01 2013) ISSN: 1464-3391 [Electronic] England
• PMID: 23199482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

• Amino Acid Sequence
• Antineoplastic Agents (pharmacology)
• Carrier Proteins (chemistry, 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, pharmacology)