Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei

Dillon Magnus T.; Barker Holly E.; Pedersen Malin; Hafsi Hind; Bhide Shreerang A.; Newbold Kate L.; Nutting Christopher M.; McLaughlin Martin; Harrington Kevin J.

首页> 外文期刊>Molecular cancer therapeutics >Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei

【24h】

Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei

机译：ATR抑制剂AZD6738通过产生腺分子微核辐射敏化

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

AZD6738 is an orally active ATR inhibitor (ATRi) currently in phase I clinical trials. We found in vitro growth inhibitory activity of this ATRi in a panel of human cancer cell lines. We demonstrated radiosensitization by AZD6738 to single radiation fractions in multiple cancer cell lines independent of both p53 and BRCA2 status by the clonogenic assay. Radiosensitization by AZD6738 to clinically relevant doses of fractionated radiation was demonstrated in vitro using a 3D tumor spheroid model and, in vivo, AZD6738 radiosensitized by abrogating the radiation-induced G2 cell-cycle checkpoint and inhibiting homologous recombination. Mitosis with damaged DNA resulted in mitotic catastrophe as measured by micronucleus formation by live-cell fluorescent-ubiquitination cell-cycle imaging of cell-cycle progression and nuclear morphology. Induction of micronuclei was significantly more prominent for AZD6738 compared with inhibition of the downstream kinase CHK1 alone at iso effective doses. Micronuclei were characterized as acentric chromosomal fragments, which displayed characteristics of increased DNA damage and cell-cycle dyssynchrony when compared with the primary nucleus. (C) 2016 AACR.

机译：AZD6738是目前在I期临床试验中的口服活性ATR抑制剂（ATRI）。我们在人类癌细胞系中发现该ATRI的体外生长抑制活性。我们将AZD6738的辐射敏化症证明了AZD6738在多种癌细胞系中的单个辐射级分，与克隆源测定的P53和BRCA2状态无关。使用3D肿瘤球体模型和体内AZD6738通过消除辐射诱导的G2细胞循环检查点并抑制同源重组，在体外进行AZD6738对临床相关的分级辐射的临床相关剂量的分级辐射剂量的分级辐射。受损DNA损坏的含量导致通过微细胞荧光 - 泛素 - 泛素 - 泛素循环循环成像和核形态学通过微细胞形成测量的有丝分裂灾难。与AZD6738相比，微核诱导显着更突出，而单独在ISO有效剂量下抑制下游激酶CHK1。微核表征为腺分子染色体片段，其与原核相比，显示出增加DNA损伤和细胞周期的特性的特征。（c）2016 AACR。

著录项

来源
《Molecular cancer therapeutics》 |2017年第1期|共10页
作者
Dillon Magnus T.; Barker Holly E.; Pedersen Malin; Hafsi Hind; Bhide Shreerang A.; Newbold Kate L.; Nutting Christopher M.; McLaughlin Martin; Harrington Kevin J.;
展开▼
作者单位

Inst Canc Res Div Radiotherapy &

Imaging Targeted Therapy Team London England;

Inst Canc Res Div Radiotherapy &

Imaging Targeted Therapy Team London England;

Inst Canc Res Div Radiotherapy &

Imaging Targeted Therapy Team London England;

Inst Canc Res Div Radiotherapy &

Imaging Targeted Therapy Team London England;

Royal Marsden Hosp London England;

Royal Marsden Hosp London England;

Royal Marsden Hosp London England;

Inst Canc Res Div Radiotherapy &

Imaging Targeted Therapy Team London England;

Inst Canc Res Div Radiotherapy &

Imaging Targeted Therapy Team London England;

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类肿瘤学;
关键词

相似文献

外文文献
中文文献
专利

1. Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei [J] . Dillon Magnus T., Barker Holly E., Pedersen Malin, Molecular cancer therapeutics . 2017,第1期

机译：ATR抑制剂AZD6738通过产生腺分子微核辐射敏化
2. LC-MS/MS assay for the simultaneous quantitation of the ATM inhibitor AZ31 and the ATR inhibitor AZD6738 in mouse plasma [J] . Kiesel Brian F., Shogan Jeffrey C., Rachid Madani, Journal of Pharmaceutical and Biomedical Analysis: An International Journal on All Drug-Related Topics in Pharmaceutical, Biomedical and Clinical Analysis . 2017,第期

机译：LC-MS / MS测定用于同时定量ATM抑制剂AZ31和ATR抑制剂AZD6738在小鼠等离子体中的抑制剂AZD6738
3. Development and Scale-up of a Route to ATR Inhibitor AZD6738 [J] . Goundry William R. F., Dai Kuangchu, Gonzalez Miguel, Organic process research & development . 2019,第7期

机译：ATR抑制剂AZD6738途径的开发和扩展
4. The Discovery and Development of Second-Generation Matrix Metalloproteinase Inhibitors for the Treatment of Cancer [C] . Andy Baxter, John Montana American Chemical Society . 2001

机译：第二代基质金属蛋白酶抑制剂的发现与发展治疗癌症
5. Radiosensibilisierung Humaner Tumorzelllinien Unterschiedlicher Entit?ten Durch Den MEK-Inhibitor PD184352 Allein Oder in Kombination mit dem HSP90-Inhibitor NVP-AUY922: Einfluss der Behandlungsschemas =Radiosensitization of Human Tumor Cell Lines of Diff [D] . Grabenbauer, Felix. 2021

机译：单独的MEK抑制剂PD184352或与HSP90抑制剂NVP-AUY922组合的不同实体的人肿瘤细胞系的放射敏化：治疗方案的影响=差异的人肿瘤细胞系的放射敏感性
6. Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei [O] . Magnus T. Dillon, Holly E. Barker, Malin Pedersen, -1

机译：ATR抑制剂AZD6738通过产生偏心微核引起的放射增敏作用
7. LC–MS/MS assay for the simultaneous quantitation of the ATM inhibitor AZ31 and the ATR inhibitor AZD6738 in mouse plasma [O] . Brian F. Kiesel, Jeffrey C. Shogan, Madani Rachid, 2017

机译：LC-MS / MS测定用于同时定量ATM抑制剂AZ31和ATR抑制剂AZD6738在小鼠等离子体中的抑制剂AZD6738

Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei

摘要

著录项

相似文献

相关主题

期刊订阅