TrxR and Angiogenesis Inhibitor(Freie Universität Berlin)(TrxR and Angiogenesis Inhibitor(Freie Universität Berlin))

概要

基本信息

药物类型

小分子化药

别名

[N-(N',N'-dimethylaminoethyl)-1,8-naphthalimide-4-sulfide](triethylphosphine)gold(I)、gold(I)(Freie Universität Berlin)

靶点

TrxR

作用机制

TrxR抑制剂(硫氧还蛋白还原酶抑制剂)、血管生成抑制剂

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Freie Universität Berlin

在研机构

Freie Universität Berlin

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 TrxR and Angiogenesis Inhibitor(Freie Universität Berlin) 相关的临床结果

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100 项与 TrxR and Angiogenesis Inhibitor(Freie Universität Berlin) 相关的转化医学

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100 项与 TrxR and Angiogenesis Inhibitor(Freie Universität Berlin) 相关的专利（医药）

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1

项与 TrxR and Angiogenesis Inhibitor(Freie Universität Berlin) 相关的文献（医药）

Nature Communications

The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity

Article

作者: Zhang, Junran ; Zhong, Yaogang ; Wang, Qi-En ; Li, Zaibo ; Guo, Deliang ; Singh, Deepika ; Yan, Chunhong ; Kim, Baek ; Zheng, Qingfei ; Prasad, Chandra Bhushan ; Li, Na ; Liu, Yujie ; Qiu, Zhaojun ; Xin, Xiwen ; Cho, Young-Jae ; Zhang, Xiaoli ; Oo, Adrian

AbstractCheckpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i’s) in combination with chemotherapy have shown promising results in preclinical studies but have displayed minimal efficacy with substantial toxicity in clinical trials. To explore combinatorial strategies that can overcome these limitations, we perform an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identify thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a determinant of CHK1i sensitivity. We establish a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR inhibitor auranofin, an approved anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, we show a pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.

100 项与 TrxR and Angiogenesis Inhibitor(Freie Universität Berlin) 相关的药物交易

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