T‐17, a novel cyclin‐dependent kinases/histone deacetylases dual inhibitor, induces cancer cells death through cell cycle arrest and apoptosis
T‐17, a novel cyclin‐dependent kinases/histone deacetylases dual inhibitor, induces cancer cells death through cell cycle arrest and apoptosis
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T-17 是一种新型细胞周期蛋白依赖性激酶/组蛋白脱乙酰酶双重抑制剂，通过细胞周期停滞和细胞凋亡诱导癌细胞死亡
DOI：
10.1002/ddr.21977
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发表时间：
2022-07
影响因子：
3.8
通讯作者：
Zongjie Gan
中科院分区：
文献类型：
--
作者：
Lin Zhang;Rui Long;Xiaoli Li;Junhao Jiang;Huali Chen;Binghua Tian;Binyu Long;Yu Yu;Zongjie Gan
细胞周期蛋白依赖性激酶（CDK）和组蛋白脱乙酰酶（HDAC）抑制剂的组合可能在抑制癌细胞增殖方面具有统计学协同作用。本文设计、合成并评价了一种新型CDKs/HDACs双重抑制剂T-17。我们的研究结果表明，T-17同时对CDKs（IC 50 = 18.0 nM）和HDAC（IC 50 = 6.6 nM）显示出有效和平衡的抑制活性，并对四种癌细胞系显示出良好的细胞活力抑制作用。T-17可使MDA-MB-231和A549细胞周期分别阻滞于G1期和S期。此外，T-17还可诱导MDA-MB-231细胞凋亡，并抑制HDAC和CDKs介导的信号通路。最后，我们还发现T-17具有良好的体内抗肿瘤活性。综上所述，这些结果表明T-17是一个有前途的先导化合物，值得进一步研究。
Combination of cyclin-dependent kinases (CDKs) and histone deacetylases (HDACs) inhibitors may have statistical synergy in suppressing cancer cell proliferation. Herein, a novel CDKs/HDACs dual inhibitor T-17 was rationally designed, synthesized, and evaluated. Our results demonstrated that T-17 concurrently exhibited potent and balanced inhibitory activity against CDKs (IC50 = 18.0 nM) and HDACs (IC50 = 6.6 nM) and also displayed good cell viability inhibitory effect on four cancer cell lines. Meanwhile, T-17 blocked the MDA-MB-231 and A549 cell cycle at G1 phase and S phase, respectively. In addition, T-17 induced MDA-MB-231 cells apoptosis and inhibited the HDACs and CDKs mediated signaling pathways. Finally, we also found that T-17 had good antitumor activity in vivo. In summary, these results indicated that T-17 would be a promising lead compound which deserves further research.
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新型聚（ADP-核糖）聚合酶-1 抑制剂 DDHCB 通过合成致死机制在体外和体内抑制 BRCA 突变乳腺癌细胞的增殖。
影响因子：
4.1
作者：
Wang Lijun;Zhang Shuhong;Yu Xuemin;Guo Chuanlong
通讯作者：
Guo Chuanlong
DOI：
10.1016/j.biopha.2016.10.057
发表时间：
2016-12
期刊：
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子：
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作者：
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通讯作者：
Lubna Wasim;Madhu Chopra
影响因子：
2.7
作者：
Yu Yu-Yu;Dongzhi Ran;junhao jiang;Tao Pan;Yanrong Dan;Q. Tang;Wei Li;Lin Zhang;Linling Gan;Zongjie Gan
通讯作者：
Yu Yu-Yu;Dongzhi Ran;junhao jiang;Tao Pan;Yanrong Dan;Q. Tang;Wei Li;Lin Zhang;Linling Gan;Zongjie Gan
影响因子：
7.3
作者：
Tang, Guozhi;Nikolovska-Coleska, Zaneta;Wang, Shaomeng
通讯作者：
Wang, Shaomeng
影响因子：
7.3
作者：
T. Liang;Yi Zhou;Reham M. Elhassan;Xuben Hou;Xinying Yang;H. Fang
通讯作者：
T. Liang;Yi Zhou;Reham M. Elhassan;Xuben Hou;Xinying Yang;H. Fang