Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells.
Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells.
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DOI：
10.3389/fphar.2021.640949
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发表时间：
2021
影响因子：
5.6
通讯作者：
Song Z
中科院分区：
文献类型：
--
作者：
Ma P;Jia G;Song Z
赖氨酸特异性去甲基化酶1（KDM 1A）通常在多种癌组织中高度表达，并通过多种细胞信号通路促进癌症的发生和发展。因此，KDM 1A是一个很有前途的药物靶点，寻找有效的KDM 1A抑制剂是至关重要的，但目前还没有一种KDM 1A抑制剂进入市场。在化合物库的帮助下，monobenzone是一种局部脱色剂，临床上用于治疗过度色素沉着，被鉴定为有效的KDM 1A抑制剂（IC 50 = 0.4507 μM），其可以可逆地竞争性抑制KDM 1A。进一步的细胞学研究证实，莫诺苯宗可抑制胃癌细胞株MGC-803和BGC-823的增殖，IC 50分别为7.82 ± 0.55 μM和6.99 ± 0.51 μM，并能清除KDM 1A、H3 K4 me 1/2和H3 K9 me 2的底物，通过逆转上皮间质转化（EMT）抑制胃癌细胞的迁移。由于莫诺苯宗的结构非常简单和小，该研究为KDM 1A抑制剂的进一步优化提供了一个新的骨架，并赋予莫诺苯宗潜在的新应用。
Lysine-specific demethylase1 (KDM1A) is generally highly expressed in various cancer tissues, and promotes the initiation and development of cancers via diverse cellular signaling pathways. Therefore, KDM1A is a promising drug target in many cancers, and it is crucial to find effective KDM1A inhibitors, while none of them has entered into market. With the help of compound library, monobenzone, a local depigmentor using as a treating over-pigmentation in clinic, was characterized as an effective KDM1A inhibitor (IC50 = 0.4507 μM), which may competitively inhibit KDM1A reversibly. Further cellular study confirmed that monobenzone could inhibit the proliferation of gastric cancer cell lines MGC-803 and BGC-823 with IC50 as 7.82 ± 0.55 μM and 6.99 ± 0.51 μM, respectively, and erase the substrate of KDM1A, H3K4me1/2 and H3K9 me2, and inhibit the migration of gastric cancer cell by reversing epithelial–mesenchymal transition (EMT). As the structure of monobenzone is very simple and small, this study provides a novel backbone for the further optimization of KDM1A inhibitor and gives monobenzone potential new application.
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影响因子：
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