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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

ND-16：一种通过靶向 JAK2 抑制皮肤 T 细胞淋巴瘤生长的新型化合物

卷 22, 期 4, 2022

发表于: 10 March, 2022

页: [328 - 339] 页: 12

弟呕挨: 10.2174/1568009622666220225121009

价格: $65

摘要

目的：皮肤T细胞淋巴瘤（CTCL）是一种临床上无法治愈的结外非霍奇金T细胞淋巴瘤。 CTCL 患者的 JAK2 扩增使其成为 CTCL 治疗的潜在靶点。在本研究中，我们旨在评估新型尼罗替尼衍生物 ND-16 对 CTCL 细胞的抗癌作用以及靶向 JAK2 的潜在机制。 方法与结果：我们发现ND-16能够调节JAK2并对CTCL H9细胞具有选择性抑制作用。表面等离子体共振和分子对接研究表明 ND-16 以高结合亲和力与 JAK2 结合。进一步研究表明，ND-16 抑制 JAK2 的下游级联反应，包括 STATs、PI3K/AKT/mTOR 和 MAPK 通路，然后调节 Bcl-2 家族成员和细胞周期蛋白 CDK/-Cyclins。流式细胞术分析证实了这些结果，ND-16 处理的 H9 细胞在 S 期显示细胞凋亡和细胞周期停滞。 结论：ND-16 可能对治疗 CTCL 具有潜在价值。

关键词: 皮肤 T 细胞淋巴瘤，ND-16，JAK2，生长，新化合物，细胞凋亡。

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