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

• Published in: Bioorganic & medicinal chemistry Vol. 21; no. 1; pp. 311 - 320
• Main Authors: Tsukuda, Senko, Kusayanagi, Tomoe, Umeda, Eri, Watanabe, Chihiro, Tosaki, Yu-ta, Kamisuki, Shinji, Takeuchi, Toshifumi, Takakusagi, Yoichi, Shiina, Isamu, Sugawara, Fumio
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.01.2013; Elsevier
• Subjects: Akt; AKT protein; Amino Acid Sequence; Antineoplastic Agents - pharmacology; bacteriophages; Biochemistry & Molecular Biology; breast neoplasms; Cancer; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Cell Line, Tumor; Cell Surface Display Techniques; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Estrogen receptors; GIGYF2; Humans; Life Sciences & Biomedicine; mechanism of action; Molecular Sequence Data; Phage display; Pharmacology & Pharmacy; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Physical Sciences; Proto-Oncogene Proteins c-akt - metabolism; Pyrrolidines - pharmacology; Ridaifen B; Science & Technology; Signal Transduction - drug effects; Tamoxifen; Tamoxifen - analogs & derivatives; Tamoxifen - pharmacology; Tumors; Phage display; Akt; Tamoxifen; GIGYF2; Ridaifen B; ACTIVATION; INDUCED APOPTOSIS; INVOLVEMENT; CARBOXYLIC ESTERS; KINASE-B; BREAST-CANCER CELLS; BENZOIC ANHYDRIDE; AKT PATHWAY; RECEPTORS
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2012.10.037

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.