Ridaifen G, tamoxifen analog, is a potent anticancer drug working through a combinatorial association with multiple cellular factors.
Ridaifen G, tamoxifen analog, is a potent anticancer drug working through a combinatorial association with multiple cellular factors.
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DOI：
10.1016/j.bmc.2015.08.001
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发表时间：
2015-09
影响因子：
3.5
通讯作者：
K. Ikeda;Shinji Kamisuki;Shoko Uetake;Akihito Mizusawa;Nozomi Ota;Tatsuki Sasaki;Senko Tsukuda;Tomoe Kusayanagi;Yoichi Takakusagi;K. Morohashi;T. Yamori;S. Dan;Isamu Shiina;F. Sugawara
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文献类型：
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作者：
K. Ikeda;Shinji Kamisuki;Shoko Uetake;Akihito Mizusawa;Nozomi Ota;Tatsuki Sasaki;Senko Tsukuda;Tomoe Kusayanagi;Yoichi Takakusagi;K. Morohashi;T. Yamori;S. Dan;Isamu Shiina;F. Sugawara
Ridaifen-G （RID-G）是我们之前合成的他莫昔芬类似物，对多种癌细胞系具有有效的生长抑制活性。他莫昔芬是一种抗癌药物，已知作用于雌激素受体（ER）和其他蛋白质。然而，有趣的是，我们之前的研究表明RID-G的作用机制与他莫昔芬不同。为了研究RID-G的分子作用模式，我们开发了一种新的化学遗传方法，将噬菌体显示屏幕与39种癌细胞系的药物效力和基因表达谱的统计分析相结合。该方法在RID-G中的应用表明，钙调蛋白（CaM）、异质核糖核蛋白A2/B1 （hnRNP A2/B1）和锌指蛋白638 （ZNF638）是RID-G的直接靶点候选蛋白。此外，RID-G易感细胞系显示出相似的RID-G靶基因表达谱。这些结果表明，RID-G的生长抑制活性涉及CaM、hnRNP A2/B1和ZNF638。
Ridaifen-G (RID-G), a tamoxifen analog that we previously synthesized, has potent growth inhibitory activity against various cancer cell lines. Tamoxifen is an anticancer drug known to act on an estrogen receptor (ER) and other proteins. However, our previous studies interestingly suggested that the mechanism of action of RID-G was different from that of tamoxifen. In order to investigate the molecular mode of action of RID-G, we developed a novel chemical genetic approach that combined a phage display screen with a statistical analysis of drug potency and gene expression profiles in thirty-nine cancer cell lines. Application of this method to RID-G revealed that three proteins, calmodulin (CaM), heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1), and zinc finger protein 638 (ZNF638) were the candidates of direct targets of RID-G. Moreover, cell lines susceptible to RID-G show similar expression profiles of RID-G target genes. These results suggest that RID-G involves CaM, hnRNP A2/B1, and ZNF638 in its growth inhibitory activity.