Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Bioorg Med Chem. 2013 Jan 1;21(1):311-20. doi: 10.1016/j.bmc.2012.10.037. Epub 2012 Oct 29.
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.
瑞达芬 B（RID-B）是一种他莫昔芬衍生物，能够强烈抑制乳腺癌的生长。有报道称，RID-B 对多种雌激素受体（ER）阳性的人类癌细胞具有抗增殖活性。有趣的是，即使对于一些 ER 阴性的细胞，RID-B 也被报道具有比他莫昔芬更高的效力，提示其具有 ER 非依赖性的作用机制。在这项研究中，T7 噬菌体展示筛选和随后的结合分析鉴定了 Grb10 相互作用 GYF 蛋白 2（GIGYF2）是 RID-B 的结合蛋白。通过细胞测定法，发现 RID-B 存在时，由 GIGYF2 介导的 Akt 磷酸化水平降低。
