Diffuse large B-cell lymphoma is the commonest type of aggressive non-Hodgkin's lymphoma, a type of cancer of a cell called a lymphocyte which makes up part of the immune system. Although most patients are cured with chemotherapy used as initial treatment, about 20-30% of patients still experience relapse. Curing relapsed disease is much less successful, even with the use of high doses of chemotherapy and stem cell transplant. There is then an urgent need for effective, new agents to treat patients with diffuse large B-cell lymphoma who have relapsed or who have developed resistance to other forms of chemotherapy.
This trial is using a drug called AZD1152 which interferes with the ability of a cancer cell to divide and grow. It has been used before in patients with other types of cancer, but never before in lymphoma patients. Responses in other cancers have been seen, particularly in leukaemia which is a disease related to lymphoma. The investigators are planning to use this agent in 15 patients with diffuse large B-cell lymphoma in which potentially curative treatments have failed. The main aim is to see whether the drug shows any activity in this type of lymphoma. This will be mainly assessed using CT and PET scans. The investigators are also investigating how well a blood test can predict both the response to the drug and the toxicity of the drug - this is called a biomarker study and forms part of the clinical trial. The other main aim of the study is to assess the toxicity of the treatment. Previous studies in humans suggest the drug is reasonably well tolerated, although side effects such as stomatitis (soreness of the mouth) and suppression of the bone marrow (leading to risk of infection and bleeding) have been seen.

开始日期2011-09-01

申办/合作机构

Oxford University Hospitals NHS Trust

[+2]

EUCTR2010-022812-37-GB

/ Not yet recruiting临床2期IIT

A phase 2 trial of AZD1152 in relapsed/refractory diffuse large B-cell lymphoma - AZD1152 in diffuse large B-cell lymphoma

开始日期2011-06-07

申办/合作机构

Oxford University Hospitals NHS Trust

NCT01019161

/ Completed临床1期

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

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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125

项与 Barasertib 相关的文献（医药）

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

BACKGROUNDLupus 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.METHODSAZD1152, 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.FINDINGSAZD1152 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.INTERPRETATIONThis 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.FUNDINGA full list of funding sources can be found in the acknowledgements section.

2025-01-01·Neoplasia

Aurora kinase B is required for growth and expansion of medulloblastoma cells in the tissue context

Article

作者: Zhang, Hanqing ; Allalou, Amin ; Neuhauss, Stephan C F ; Neuhauss, Stephan C.F. ; Özalp, Özgün ; Santhana Kumar, Karthiga ; Grotzer, Michael A. ; Baumgartner, Martin ; Gries, Alexandre ; Kuttler, Fabien ; Grotzer, Michael A ; Akle, Veronica

The impact of the tissue context on tumor growth and drug response in medulloblastoma (MB) is poorly understood. To gain insights into the growth and dissemination behavior of the MB tumor cells under treatment, we combined three-dimensional cell culture screening with ex vivo organotypic cerebellum slice co-culture (OCSC), which allowed the assessment of tumor cell behavior in the tissue context. To identify druggable kinase pathways involved in invasion, we screened a panel of 274 kinase inhibitors and identified aurora kinase B (AURKB) as a potential anti-invasion drug target in MB. We validated tumor suppressive activities of the AURKB inhibitor (AURKBi) Barasertib (AZD1152-HQPA) and the structurally unrelated compound GSK-1070916 in cerebellum slice culture models for SHH, and Grp3 MB. Importantly, AURKBi are tumor suppressive in the tissue context, also in MB tumor cells that are in vitro resistant to the same treatment. We confirmed the requirement of AURKB for tumor growth and expansion in the tissue context through genetic suppression of AURKB by siRNA. We revealed that the combination of AURKBi with the SRC/BCR-ABL inhibitor Dasatinib acts synergistically to repress tumor growth and expansion in the highly invasive MB cell model ONS-76, but not in Grp3 MB cells. We demonstrate that tumor growth in the tissue context is suppressed by pharmacological inhibition of AURKB, comparable to the growth reduction observed after X-ray irradiation, which was used as the positive control. Finally, we show that exposure to µM concentrations of Barasertib does not cause developmental toxicity in fish larvae. In conclusion, we demonstrate that AURKB is essential for MB tumor growth and expansion in the tissue context and the inhibition of AURKB is equally efficient as irradiation in repressing tumor cell growth. In patients younger than three years, pharmacological targeting of AURKB may thus constitute a novel means to overcome radiotherapy limitations.

2024-11-22·JCI Insight

Cell cycle inhibitors activate the hypoxia-induced DDX41/STING pathway to mediate antitumor immune response in liver cancer

Article

作者: Wong, Carmen Chak Lui ; Zhang, Misty Shuo ; Goh, Chi Ching ; Tse, Aki Pui Wah ; Cheu, Jacinth Wing Sum ; Zhang, Yan ; Wong, Po Yee ; Xue, Helen Do Gai ; Chan, Cerise Yuen Ki

Cell cycle inhibitors have a long history as cancer treatment. Here, we report that these inhibitors combated cancer partially via the stimulator of IFN genes (STING) signaling pathway. We demonstrated that paclitaxel (microtubule stabilizer), palbociclib (cyclin-dependent kinase 4/6 inhibitor), and AZD1152 and GSK1070916 (aurora kinase B inhibitors) have anticancer functions beyond arresting the cell cycle. They consistently caused cytosolic DNA accumulation and DNA damage, which inadvertently triggered the cytosolic DNA sensor DEAD-box helicase 41 (DDX41) and activated STING to secrete pro-inflammatory senescence-associated secretory phenotype factors (SASPs). Interestingly, we found that DDX41 was a transcriptional target of HIF. Hypoxia induced expression of DDX41 through HIF-1, making hypoxic hepatocellular carcinoma (HCC) cells more sensitive to the antimitotic agents in STING activation and SASP production. The SASPs triggered immune cell infiltration in tumors for cancer clearance. The treatment with cell cycle inhibitors, especially paclitaxel, extended survival by perturbing mouse HCC growth when used in combination with anti-PD-1. We observed a trend that paclitaxel suppressed Sting wild-type HCC more effectively than Sting-KO HCC, suggesting that STING might contribute to the antitumor effects of paclitaxel. Our study revealed the immune-mediated tumor-suppressing properties of cell cycle inhibitors and suggested combined treatment with immunotherapy as a potential therapeutic approach.

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.libproxy1.nus.edu.sg/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

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
复发性急性髓细胞白血病	临床前	荷兰	AstraZeneca PLC	2006-05-01
复发性急性髓细胞白血病	临床前	意大利	AstraZeneca PLC	2006-05-01
复发性急性髓细胞白血病	临床前	法国	AstraZeneca PLC	2006-05-01
复发性急性髓细胞白血病	临床前	美国	AstraZeneca PLC	2006-05-01
晚期恶性实体瘤	临床前	荷兰	AstraZeneca PLC	2005-05-01
急性髓性白血病	临床前	-	阿斯利康制药有限公司	-
急性髓性白血病	临床前	-	阿斯利康制药有限公司	-
弥漫性大B细胞淋巴瘤	临床前	-	阿斯利康制药有限公司	-

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临床结果

适应症

分期

评价

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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)	製獵廠艱顧衊鑰淵鬱簾(願遞築製醖顧衊鹹蓋願) = 鏇範構願壓壓鹽願顧範餘構襯觸構觸夢齋築艱 (遞壓製壓淵糧淵願醖醖, 淵願艱襯觸構齋夢選憲 ~ 鏇鹽艱艱糧蓋築製繭網) 更多	-	2014-03-31
				LDAC (LDAC 20mg)	製獵廠艱顧衊鑰淵鬱簾(願遞築製醖顧衊鹹蓋願) = 鏇餘構膚壓憲鏇憲齋糧餘構襯觸構觸夢齋築艱 (遞壓製壓淵糧淵願醖醖, 膚齋憲鬱廠獵鹹襯鏇醖 ~ 憲構糧鹹醖範製鏇襯醖) 更多
NCT00952588 (ASCO2012)	临床2期	急性髓性白血病	74	Barasertib 1200 mg	鹽齋鹹齋顧糧衊膚積網(鏇鹹積艱鬱衊遞範鬱艱) = 構鹽廠艱艱顧夢膚願蓋壓艱憲顧顧鹹壓獵窪糧 (艱廠艱遞廠夢糧壓餘壓 ) 更多	积极	2012-05-20
				LDAC 20 mg	鹽齋鹹齋顧糧衊膚積網(鏇鹹積艱鬱衊遞範鬱艱) = 顧鬱壓餘選遞遞鏇餘鏇壓艱憲顧顧鹹壓獵窪糧 (艱廠艱遞廠夢糧壓餘壓 ) 更多