A Phase I Open, Non-randomised, Single-centre Study to Assess the Metabolism, Excretion and Pharmacokinetics of AZD1152 and AZD1152 hQPA Following Intravenous Administration of [14C]-AZD1152 in Patients With Acute Myeloid Leukaemia (AML)

The purpose of the study is to assess how AZD1152 is absorbed or excreted in and out of the body in patients with Acute Myeloid Leukaemia (AML).

开始日期2009-11-01

申办/合作机构

AstraZeneca PLC

NCT00952588

/ Completed临床2/3期

A Randomised, Open-label, Multi-centre, 2-stage, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC) in Comparison With LDAC Alone in Patients Aged ≥ 60 With Newly Diagnosed Acute Myeloid Leukaemia (AML)

The purpose of this study is to assess the efficacy, safety and tolerability of AZD1152 alone and in combination with low dose cytosine arabinoside (LDAC) in comparison with LDAC alone in AML patients.

开始日期2009-07-01

申办/合作机构

AstraZeneca PLC

EUCTR2009-010114-30-DE

/ Not yet recruitingN/A

A randomised, open-label, multi-centre, 2-stage, parallel group study to assess the efficacy, safety and tolerability of AZD1152 alone and in combination with low dose cytosine arabinoside (LDAC) in comparison with LDAC alone in patients aged = 60 with newly diagnosed acute myeloid leukaemia (AML) who are considered unsuitable to receive intensive induction chemotherapy regimens

开始日期2009-06-23

申办/合作机构

AstraZeneca AB

100 项与 Barasertib 相关的临床结果

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100 项与 Barasertib 相关的转化医学

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100 项与 Barasertib 相关的专利（医药）

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282

项与 Barasertib 相关的文献（医药）

2025-05-01·JOURNAL OF MOLECULAR GRAPHICS & MODELLING

Structural characterization of Aurora kinase B modulation by Epigallocatechin gallate: Insights from docking and dynamics simulations

Article

作者: Javali, Prashanth S ; Thirumurugan, Kavitha

Aurora Kinase B (AURKB) is crucial for chromosome alignment, segregation, and cytokinesis, phosphorylating essential proteins for accurate cell division. Mutations and overexpression of AURKB are common in various cancers. Inhibiting AURKB reduces therapy resistance, making it a promising therapeutic target. Synthetic inhibitors like AZD1152 and ZM447439 show selectivity for AURKB but often lack specificity due to high homology within the aurora kinase family. Conversely, natural molecules such as flavonoids offer selectivity, lower toxicity, and potential synergy with existing chemotherapies. Investigating natural AURKB inhibitors could lead to safer and more effective cancer treatments. Epigallocatechin-3-gallate (EGCG), a catechin ester in green tea, inhibits glioma cell line proliferation by inducing spontaneous apoptosis and reduces cancer cell invasiveness by decreasing metalloproteinase, cytokine, and chemokine activities. Additionally, EGCG inhibits several kinases, including PI3K, mTOR, EGFR, and AKT, acting as an effective ATP-competitive inhibitor. Thus, EGCG may enhance the efficacy of anti-cancer therapies as an AURKB inhibitor. This study used in silico tools to predict EGCG's pharmacodynamics and pharmacokinetics, and employed AutoDock for molecular docking with AURKB. The ligand-protein complex and Apo form of AURKB were simulated for 100 ns with GROMACS using the CHARM36 force field. Free energy surface analysis and MMPBSA methods confirmed the stability and spontaneity of EGCG binding to AURKB. The conformational dynamics of the DFG (Asp-Phe-Gly) motif in AURKB upon EGCG binding revealed significant changes crucial for ATP binding and kinase activity. The distance between the phenylalanine residue of the DFG motif and the αC helix in holo AURKB increased from 14.80 Å to 23.62 Å in the lowest free energy structure, indicating a shift from the DFG-in to the DFG-out state, affecting ATP binding. The study also noted transitions in the overall protein secondary structures, such as turn to coil, coil to sheet, and coil to helix, contributing to a stable structure upon EGCG binding. These findings highlight the complex interplay between EGCG and AURKB, providing insights into the conformational dynamics and structural alterations induced by this interaction, which has implications for reducing glioma cell chemosensitivity to therapeutic drugs.

2025-04-01·Science Bulletin

Dynamic R-loops at centromeres ensure chromosome alignment during oocyte meiotic divisions in mice

Article

作者: Liu, Chao ; Wang, Liying ; Gao, Fei ; Chen, Yinghong ; Wei, Huafang ; Wei, Wei ; Ma, Shuang ; Huang, Xiaoming ; Ma, Yanjie ; Zhou, Qiuxing ; Zhang, Meijia ; Han, Tingting ; Li, Wei

R-loops play various roles in many physiological processes, however, their role in meiotic division remains largely unknown. Here we show that R-loops and their regulator RNase H1 are present at centromeres during oocyte meiotic divisions. Proper centromeric R-loops are essential to ensure chromosome alignment in oocytes during metaphase I (MI). Remarkably, both Rnaseh1 knockout and overexpression in oocytes lead to severe spindle assembly defects and chromosome misalignment due to dysregulation of R-loops at centromeres. Furthermore, we find that replication protein A (RPA) is recruited to centromeric R-loops, facilitating the deposition of ataxia telangiectasia-mutated and Rad3-related (ATR) kinase at centromeres by interacting with the ATR-interaction protein (ATRIP). The ATR kinase deposition triggers the activity of CHK1, stimulating the phosphorylation of Aurora B to finally promote proper spindle assembly and chromosome alignment at the equatorial plate. Most importantly, the application of ATR, CHK1, and Aurora B inhibitors could efficiently rescue the defects in spindle assembly and chromosome alignment due to RNase H1 deficiency in oocytes. Overall, our findings uncover a critical role of R-loops during mouse oocyte meiotic divisions, suggesting that dysregulation of R-loops may be associated with female infertility. Additionally, ATR, CHK1, and Aurora B inhibitors may potentially be used to treat some infertile patients.

2025-02-01·EBioMedicine

Aurora kinase B inhibitor AZD1152: repurposing for treatment of lupus nephritis driven by the results of clinical trials

Article

作者: Liang, Shaoshan ; Zhang, Changming ; Lang, Yue ; Zhang, Mingchao ; Li, Ping ; Liu, Zhihong ; Jin, Xuexiao ; Zheng, Zuguo ; Zhao, Yue

BACKGROUND:

Lupus nephritis (LN) is one of the most common and severe complications of systemic lupus erythematosus (SLE). Multitarget therapy (MT) achieves a 20% higher complete remission (CR) rate compared to conventional therapy in LN management. Intrigued by its excellent clinical efficacy, we aimed to develop a single-agent therapy with comparable efficacy to MT, offering a simplified treatment regimen.

METHODS:

AZD1152, an Aurora kinase B (Aurkb) inhibitor, was identified through transcriptomic analyses and the L1000 CMap drug repurposing database. The therapeutic efficacy of AZD1152 was evaluated in MRL/lpr mice. Transcriptome sequencing and functional assays were performed to elucidate its mechanisms of action. Aurkb expression and its clinical relevance were assessed in lupus-prone mice and patients with LN.

FINDINGS:

AZD1152 significantly attenuated systemic immune activation and renal injury in MRL/lpr mice, demonstrating efficacy comparable to MT regimens in animal studies. AZD1152 treatment modulated immune-inflammatory pathways in the kidney. Aurkb expression was upregulated in T cells infiltrating the renal interstitium in LN. Additionally, Aurkb expression levels positively correlated with the activity index (AI) and serum creatinine (Scr) in patients with LN. Mechanistic studies revealed that AZD1152 exerts therapeutic effects primarily by inhibiting T-cell proliferation.

INTERPRETATION:

This study presents a drug development strategy that integrates clinically validated LN therapies with drug repurposing approaches. This strategy could accelerate drug development and clinical translation processes for LN.

FUNDING:

A full list of funding sources can be found in the acknowledgements section.

项与 Barasertib 相关的新闻（医药）

2024-07-25

·生物谷

上海交通大学于颖彦教授揭示极光激酶抑制剂诱导的胃癌类器官衰老可削弱巨噬细胞的天然免疫反应

2024年7月，于颖彦教授在《Cancer Letters》【IF9.1，Q1】杂志在线发表题名为“Drug-induced senescence by aurora kinase inhibitors attenuates innate immune response of macrophages on gastric cancer organoids.”——极光激酶抑制剂诱导的胃癌类器官衰老可削弱巨噬细胞的天然免疫反应的研究论文。瑞金医院普外科/上海消化外科研究所于颖彦教授、WHO 国际癌症研究机构Zisis Kozlakidis 教授为论文的共同通讯作者；瑞金医院普外科/上海消化外科研究所杨蕊馨博士研究生、关颖欣博士研究生为论文的共同第一作者。 doi：10.1016/j.canlet.2024.217106. 中文摘要弥漫型胃癌（DGC）以浸润性强、容易转移、预后较差而著称。研发靶向弥漫型胃癌的药物具有重要意义。该研究中，团队利用患者来源类器官（PDO）对一组小分子激酶抑制剂进行筛选，尤其关注不同亚型胃癌的敏感性差异。发现肠型胃癌（IGC）对多种激酶抑制剂敏感，而DGC显示耐药，并在极光激酶抑制剂（AURKi）巴拉塞替（Barasertib）和达努塞替（Danusertib）治疗后出现药物性肿瘤细胞衰老改变，表现为细胞体积增大，出现多核瘤巨细胞，并呈现衰老相关β-半乳糖苷酶（SA-β-GAL）染色强阳性。肿瘤细胞分泌大量的炎症趋化因子MCP-1/CCL2，诱导单核巨噬细胞聚集并发生M2极化，导致原本来杀伤肿瘤的机体天然免疫巨噬细胞杀伤力减弱。这种新型免疫抑制机制的发现提示，对于弥漫型胃癌可采用AURKi + 清除衰老肿瘤细胞的序贯治疗。 Abstract Diffuse-type gastric cancer (DGC) is a subtype of gastric cancer with aggressiveness andpoor prognosis. It is of great significance to find sensitive drugs for DGC. In the current study, a total of 20 patient-derived organoids(PDOs) were analyzed for screening the therapeutic efficacy of small molecule kinases inhibitors ongastric cancers, especially the therapeutic difference betweenintestinal-type gastric cancer (IGCs) and DGCs. The IGCs are sensitive to multiple kinases inhibitors, while DGCs are resistantto most of these kinases inhibitors. It was found that DGCs showed drug-induced senescent phenotype after treatment by aurora kinases inhibitors(AURKi) Barasertib-HQPA and Danusertib. The cell diameter of cancer cells are increased with stronger staining of senescence-associated β-galactosidase (SA-β-GAL), and characteristic appearance of multinucleated giant cells. The senescent cancer cells secrete large amounts of chemokine MCP-1/CCL2, which recruitand inducemacrophage to M2-type polarizationin PDOs of DGC (DPDOs)-macrophage co-culturesystem. The up-regulation of local MCP-1/CCL2 can interact with MCP-1/CCL2 receptor (CCR2)expressed on macrophages and suppress theirinnate immunity tocancer cells.Overall, the special response of DGC to AURKisuggests that clinicians should select a sequential therapy withsenescent cell clearanceafter AURKi treatment for DGC. 该研究首先探讨了不同亚型胃癌PDO对小分子激酶抑制剂的敏感性差异。采用96孔板对2例肠型胃癌PDO （IPDO）和4例弥漫型胃癌PDO（DPDO）筛选了11种激酶抑制剂的药物敏感性。其中IPDO对多种激酶抑制剂均敏感，而DPDO对激酶抑制剂的敏感性均较差。4例DPDO的表型均显示细胞之间黏附性较差，细胞分布杂乱无极性。采用AURKi Barasertib和Danusertib处理48小时，肿瘤细胞直径显著变大，但并没有发生明显的细胞裂解坏死，而是出现瘤巨细胞变化，高度提示为细胞衰老，遂进行了SA-β-GAL染色，证实AURKi诱导的细胞SA-β-GAL染色显著增强。在Giemsa染色下，AURKi处理组的DPDO肿瘤细胞体积显著增大，出现多核及巨核瘤巨细胞衰老表型特征。作者遂收集了经SA-β-GAL染色证实的8例早期传代活力良好类器官的培养上清和6例衰老类器官的培养上清，检测了12种炎症相关因子的含量变化。随着类器官传代次数增加，培养上清中单核巨噬细胞趋化因子MCP-1/CCL2的含量升高程度最为明显。采用AURKi处理的DPDO培养上清液也检查到高含量的MCP-1/CCL2。经过对开源数据库胃癌单细胞测序数据集（GSE163558）的细胞分群与炎症相关因子表达水平分析，在7个上皮来源细胞亚群中，C3亚群高表达衰老相关基因CDKN2A和CDKN2B，同时，MCP-1/CCL2阳性表达细胞比例最高。利用GSEA通路富集分析发现，高表达MCP-1/CCL2的C3亚群的基因集主要富集在ROS通路、蛋白质分泌通路、EMT通路和炎症反应通路等等。以集落刺激因子1受体CSF1R作为巨噬细胞标志基因，对巨噬细胞亚群进行分析发现，其M2极化巨噬细胞的MCP-1/CCL2阳性表达细胞比例最高。GSEA通路富集分析显示，M2型巨噬细胞上调的基因集主要富集在TNFα信号通路、EMT通路、促血管生成通路及蛋白质分泌通路等等。乳酸脱氢酶（LDH）释放量可以反映细胞膜的完整性，研究人员测定了DPDO-巨噬细胞共培养体系内添加rhMCP-1处理对LDH释放的影响。与对照组相比，rhMCP-1处理组的LDH释放量显著降低，表明微环境内MCP-1/CCL2的增加致使巨噬细胞对肿瘤的吞噬杀伤作用减弱。对肿瘤细胞涂片进行Giemsa染色，可见未经rhMCP-1处理的肿瘤细胞裂解增加，而rhMCP-1处理组的肿瘤细胞形态保留完整，细胞体积增大。采用siRNA干扰巨噬细胞表面的CCR2受体表达，则巨噬细胞受MCP-1/CCL2趋化因子影响减少，细胞迁移能力明显减弱。在抗癌药物筛选领域，诱发细胞衰老从而阻滞肿瘤生长是候选策略之一。然而，“老而不死”肿瘤细胞的生物学作用尚有待深入研究。近年来细胞衰老机制研究有了长足发展，衰老细胞可以通过自分泌或者旁分泌产生大量细胞因子与炎症因子,构成衰老相关分泌表型（SASP），但SASP对胃癌细胞的影响尚不清楚。该研究将类器官实验研究与外部单细胞测序数据集分析相结合，鉴定到衰老的肿瘤上皮细胞可以产生大量的MCP-1/CCL2炎症趋化因子，趋化单核巨噬细胞聚集到肿瘤周围，诱发单核巨噬细胞向M2极化，从而削弱了单核细胞吞噬杀伤肿瘤的能力。该研究与最近几项在其它类型肿瘤的研究结果不谋而合。近来已有研究显示，肿瘤细胞衰老是一种不容忽视的现象，此类细胞有可能成为肿瘤复发与转移的根源，应当积极探索靶向衰老肿瘤细胞的干预策略。针对弥漫型胃癌的这种药物反应特性，可以考虑AURKi+衰老细胞靶向清除的序贯疗法作为一种新型治疗策略。作者介绍于颖彦主任医师，教授，博士研究生导师，上海交通大学医学院附属瑞金医院普外科/上海消化外科研究所；研究方向：胃癌的基础与转化研究。杨蕊馨博士研究生，上海交通大学医学院附属瑞金医院普外科/上海消化外科研究所；研究方向：胃癌发病机制及靶向治疗。关颖欣博士研究生，上海交通大学医学院附属瑞金医院普外科/上海消化外科研究所；研究方向：胃癌发病机制及靶向治疗。【扫描二维码可下载原文】 Drug-induced senescence by aurora kinase inhibitors attenuates innate immune response of macrophages on gastric cancer organoids.pdf

临床研究

2022-12-19

·生物谷

《自然》子刊：破解癌细胞“老而不死”之谜！中国科学家找到杀死衰老癌细胞的新方法

岁月不饶人，也没饶了癌细胞。即使强如癌细胞也免不了会衰老，然而细胞衰老对肿瘤发展的影响却表现出两面性。岁月不饶人，也没饶了癌细胞。即使强如癌细胞也免不了会衰老，然而细胞衰老对肿瘤发展的影响却表现出两面性。一方面，细胞衰老持续性地阻碍了细胞周期运转，抑制肿瘤生长。另一方面，衰老细胞可以引起慢性炎症、免疫抑制并促进肿瘤细胞的间质-上皮转化，从而促进肿瘤免疫逃逸以及转移[1,2,3]。因此，虽然肿瘤细胞发生衰老代表着治疗的初步理想结果，但衰老细胞的长期存在可能是有害的。这提示我们或许可以通过化疗等手段诱导肿瘤细胞的衰老，随后通过药物清除衰老细胞避免其长期存在，给予肿瘤双重打击[4]。 Senolytics是一类可以清除衰老细胞的药物，或许可以应用于上述的治疗策略。但是目前的局限之处在于我们缺少一些特异性针对衰老肿瘤细胞的、低毒的Senolytic。近期，来自荷兰癌症研究所的René Bernards/王力勤团队和上海市肿瘤研究所覃文新团队联合在《自然·癌症》上发表研究成果[5]。他们发现衰老的肿瘤细胞会上调cFLIP表达以阻止死亡受体5（DR5）介导的细胞凋亡。而抑制溴结构域包含蛋白2（BRD2）可以减少cFLIP，使衰老的肿瘤细胞对DR5介导的凋亡更加敏感，因此联用BRD2抑制剂与DR5激动性抗体可以杀死多种衰老的肿瘤细胞。在动物模型中，“细胞衰老诱导剂+BRD2抑制剂+DR5激动性抗体”组合可以达到更好的抗肿瘤效果。论文首页截图为了寻找衰老肿瘤细胞的阿喀琉斯之踵，研究团队使用了全基因组CRISPR-Cas9敲除筛选体系，以寻找那些敲除后能够显著促进衰老肿瘤细胞死亡的基因。他们发现，在衰老诱导剂（极光激酶A抑制剂Alisertib、PLK4抑制剂CFI-400945和拓扑异构酶II抑制剂Etoposide）处理后的A549细胞中敲除CFLAR（编码cFLIP）可以显著促进衰老肿瘤细胞的死亡。接下来，研究团队通过cFLIP敲除细胞系验证了上述CRISPR-Cas9筛选的结果，并且发现敲除cFLIP是通过增加细胞凋亡的方式促进衰老肿瘤细胞死亡的。敲除cFLIP促进衰老肿瘤细胞发生caspase3/7依赖的细胞凋亡为了探究为什么敲除cFLIP之后可以促进衰老肿瘤细胞的凋亡，研究团队对经过Alisertib处理的A549细胞进行转录组测序以及分析。他们发现，衰老的肿瘤细胞中NF-κB信号显著增强，而cFLIP正是NF-κB的下游基因。Q-PCR结果表明，衰老的肿瘤细胞中cFLIP、死亡受体DR5及其配体TRAIL等多种NF-κB下游基因mRNA显著增加。这一现象在多种肿瘤细胞中普遍存在。由于cFLIP具有抑制DR5介导的细胞凋亡的作用[6]，研究团队猜想，NF-κB活性在衰老细胞中上调，这导致DR5及其配体TRAIL的表达增加，从而引发衰老细胞凋亡。然而，随着cFLIP的增加，衰老细胞免于凋亡。衰老肿瘤细胞中NF-κB活性增强，cFLIP、DR5和TRAIL表达增加既然衰老的肿瘤细胞会上调表达DR5，那么使用TRAIL处理是否可以促进衰老肿瘤细胞的死亡呢？研究团队使用重组三聚体TRAIL蛋白处理衰老的肿瘤细胞，发现这可以显著地促进衰老肿瘤细胞的凋亡，并且这种作用依赖于DR5。由于TRAIL的生物利用率很低，并且会被诱饵受体结合，研究团队尝试使用DR5的激动性抗体conatumumab处理衰老肿瘤细胞。他们发现，conatumumab通过引起细胞凋亡选择性杀死衰老肿瘤细胞。 TRAIL以及DR5激动性抗体可以选择性清除衰老的肿瘤细胞为了探究conatumumab能否应用在“诱导肿瘤细胞衰老—清除衰老细胞”抗肿瘤策略中，研究团队构建了肝细胞癌患者来源的异种移植 (PDX) 模型，并给予小鼠Alisertib、Barasertib（两种细胞衰老诱导剂）以及conatumumab单药治疗或者组合治疗。他们发现，单用时仅Alisertib有一定疗效，但是将conatumumab与Alisertib或Barasertib联合使用则可以显著改善治疗效果。肿瘤组织样本检测发现，Alisertib治疗可以诱导肿瘤细胞衰老，而在联合治疗组中，肿瘤内衰老细胞的比例显著降低。这表明联合治疗清除了衰老的肿瘤细胞并显著改善了抗肿瘤治疗效果。将DR5激动性抗体与衰老诱导剂联用显著增强抗肿瘤治疗效果由于几种DR5激动性抗体在临床上显示出较多的毒副作用[7]，因此研究团队希望继续改进治疗策略为了进一步降低DR5的抗体用量。为此，研究团队再次进行了CRISPR/Cas9筛选，以寻找敲除后可使PC9肺癌细胞对DR5激动性抗体治疗敏感的基因。他们发现，敲除BRD2可以使肿瘤细胞对conatumumab处理更加敏感（这里用的并不是衰老肿瘤细胞，而是未经衰老诱导剂处理的细胞）。随后他们使用小分子抑制剂NEO2734证实了筛选结果。重要的是，使用能够杀死肿瘤细胞的相同药物浓度的conatumumab和NEO2734并不会杀死人类原代视网膜细胞（Rep1）和成纤维细胞（BJ），表明这种联合用药策略能够显著降低毒副作用。不过，为何抑制BRD2可以增加肿瘤细胞对DR5激动性抗体的敏感性呢？为了探究这个问题，研究团队对NEO2734处理的肿瘤细胞进行了转录组分析。他们发现，NEO2734处理能够显著降低cFLIP的表达。这与之前在衰老细胞中进行的CRISPR筛选结果一致，所以研究团队测试了BRD2抑制剂与DR5激动性抗体联合处理是否能够有效清除衰老肿瘤细胞。结果显示，低剂量的BRD2抑制剂与DR5激动性抗体处理优先清除了衰老的肿瘤细胞。抑制BRD2降低cFLIP的表达并增强肿瘤细胞对DR5激动性抗体的敏感性；BRD2抑制剂+DR5激动性抗体可以有效并优先清除衰老肿瘤细胞最后，研究团队在小鼠体内探究了“细胞衰老诱导剂+BRD2抑制剂+DR5激动性抗体”组合的抗肿瘤效果。结果显示，单药治疗有一定的抑制肿瘤生长效果，但是三药联用极大地改善了治疗效果。 “细胞衰老诱导剂+BRD2抑制剂+DR5激动性抗体”药物组合能够有效抑制肿瘤生长这项研究成果显示，衰老肿瘤细胞中死亡受体DR5及其配体TRAIL上调，说明衰老肿瘤细胞已经为死亡做好了准备，但是cFLIP抑制了肿瘤细胞的凋亡。抑制BRD2，可以降低肿瘤细胞内cFLIP的表达，使肿瘤细胞对DR5介导的细胞凋亡更加敏感。因此，将细胞衰老诱导剂、BRD2抑制剂以及DR5激动剂联用可以十分有效地清除肿瘤细胞。此外，这项研究成果也表明，肿瘤细胞内NF-κB活性增加可能代表着其为死亡做好了准备（DR5以及TRAIL上调），只是cFLIP阻碍了其死亡。因此，抑制BRD2或许对一些NF-κB 驱动的肿瘤具有治疗作用。参考文献： 1.Kuilman, T. et al Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019–1031 (2008) 2.Demaria, M. et al Cellular senescence promotes adverse efects of chemotherapy and cancer relapse. Cancer Discov. 7, 165–176 (2017) 3.Faget, D. V., Ren, Q. & Stewart, S. A. Unmasking senescence: context-dependent efects of SASP in cancer. Nat. Rev. Cancer 19, 439–453 (2019) 4.Wang L, Lankhorst L, Bernards R. Exploiting senescence for the treatment of cancer. Nat Rev Cancer. 2022;22(6):340-355. doi:10.1038/s41568-022-00450-9 5.Wang, L., Jin, H., Jochems, F. et al. cFLIP suppression and DR5 activation sensitize senescent cancer cells to senolysis. Nat Cancer 3, 1284–1299 (2022). https://doi.org/10.1038/s43018-022-00462-2 6.Shirley S, Micheau O. Targeting c-FLIP in cancer. Cancer Lett. 2013;332(2):141-150. doi:10.1016/j.canlet.2010.10.009 7. Finnberg, N. K. et al Agonists of the TRAIL death receptor DR5 sensitize intestinal stem cells to chemotherapy-induced cell death and trigger gastrointestinal toxicity. Cancer Res. 76, 700–712 (2016).

免疫疗法信使RNA

100 项与 Barasertib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11747

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性髓性白血病	临床3期	美国	AstraZeneca PLC	2009-07-01
急性髓性白血病	临床3期	日本	AstraZeneca PLC	2009-07-01
急性髓性白血病	临床3期	澳大利亚	AstraZeneca PLC	2009-07-01
急性髓性白血病	临床3期	法国	AstraZeneca PLC	2009-07-01
急性髓性白血病	临床3期	德国	AstraZeneca PLC	2009-07-01
急性髓性白血病	临床3期	意大利	AstraZeneca PLC	2009-07-01
急性髓性白血病	临床3期	罗马尼亚	AstraZeneca PLC	2009-07-01
急性髓性白血病	临床3期	西班牙	AstraZeneca PLC	2009-07-01
急性髓性白血病	临床3期	英国	AstraZeneca PLC	2009-07-01
复发性急性髓细胞白血病	临床1期	美国	AstraZeneca PLC	2006-05-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00952588 (SPARK-AML1, CTgov)	临床2/3期	急性髓性白血病	74	AZD1152 (AZD1152 1200mg)	淵夢鏇廠餘鏇選顧壓範 = 壓顧醖鹽鏇鬱製獵廠鏇壓膚窪構顧壓製願構鏇 (膚窪範廠衊願糧鬱齋築, 製憲鹽鏇夢衊蓋觸醖襯 ~ 艱繭淵繭鹽憲憲繭膚鏇) 更多	-	2014-03-31
NCT00952588 (SPARK-AML1, CTgov)	临床2/3期	急性髓性白血病	74	LDAC (LDAC 20mg)	淵夢鏇廠餘鏇選顧壓範 = 醖構鏇繭壓艱積鏇餘鑰壓膚窪構顧壓製願構鏇 (膚窪範廠衊願糧鬱齋築, 遞鏇鏇鹽願鹹糧艱遞選 ~ 鹽廠餘築繭憲獵蓋選夢) 更多	-	2014-03-31
NCT00497991 (Pubmed \| Blood)	临床1/2期	急性髓性白血病	32	Barasertib	顧範網顧壓膚願鹽積憲(繭顧鹹繭襯夢醖醖齋淵) = 憲願齋鬱願範繭窪廠選觸憲築鬱築鑰衊願艱觸 (製遞願築窪淵製淵齋築 )	-	2011-12-01