更新于：2024-04-22

Tamoxifen Citrate

枸橼酸他莫昔芬

更新于：2024-04-22

概要

概要

基本信息

药物类型

小分子化药

别名

(Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamine、(Z)-2-(para-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylamine、1-p-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene

+ [14]

靶点

作用机制

ERs拮抗剂(雌激素受体家族拮抗剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Rosemont Pharmaceuticals Ltd.

+ [1]

非在研机构

AstraZeneca PLCAstraZeneca Pharmaceuticals LP

最高研发阶段批准上市

首次获批日期

美国 (1977-12-30),

乳腺癌

最高研发阶段(中国)批准上市

特殊审评孤儿药 (欧盟)

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结构

分子式C32H37NO8

InChIKeyFQZYTYWMLGAPFJ-OQKDUQJOSA-N

CAS号54965-24-1

关联

390

项与枸橼酸他莫昔芬相关的临床试验

NCT06364267 / Not yet recruiting临床2期

Randomized Double Blind Phase 2 Trial of Baby Tamoxifen Versus Baby Exemestane in Post-menopausal Women at High Risk for Breast Cancer. BabyTEARS (Baby Tamoxifen or Exemestane Assessment Randomized Study)

The purpose of the study is to determine if 6 and 12 months of treatment with Tamoxifen at lower dose is superior to Exemestane at lower dose on quality of life.

开始日期2024-09-01

申办/合作机构

Ente Ospedaliero Ospedali Galliera

[+3]

NCT06184750 / Not yet recruiting临床2期IIT

Refining Tamoxifen Dose for Premenopausal Breast Cancer Risk Reduction (RENAISSANCE): A Phase II Single Arm Trial

This phase II trial evaluates response-guided low-dose tamoxifen for reducing breast density in women who are at higher than average risk for breast cancer. Increasing breast density is a well established risk factor for breast cancer. Tamoxifen is a selective estrogen receptor modulator. It works by blocking the effects of the hormone estrogen in the breast. Tamoxifen has been shown to reduce breast density, even at reduced dosages, and is approved for the prevention of breast cancer.

开始日期2024-08-03

申办/合作机构

National Cancer Institute

NCT06361940 / Not yet recruiting临床2期

Molecular Analyses to Identify Pathways of Endocrine Resistance Following Short Term Neoadjuvant Endocrine Treatment in Patients With Hormone Receptor-Positive HER2-negative Breast Cancer

This is an exploratory phase II interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for 4-12 weeks (+/- 2 weeks).

开始日期2024-08-01

申办/合作机构

The Medical College of Wisconsin, Inc.

100 项与枸橼酸他莫昔芬相关的临床结果

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100 项与枸橼酸他莫昔芬相关的转化医学

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100 项与枸橼酸他莫昔芬相关的专利（医药）

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23,509

项与枸橼酸他莫昔芬相关的文献（医药）

2106-07-05·Oncotarget

miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer

Article

作者: Lee, Yeon Seon ; Park, Jong Hoon ; Kim, Ye Sol ; Park, Sae Jeong ; Kong, Hyun Kyung

Estrogen receptor-alpha (ERα) is a clinically important therapeutic target for breast cancer. However, tumors that lose ERα are less responsive to anti-estrogens such as tamoxifen. MicroRNAs (miRNAs) are small RNAs that regulate expression of their target gene and dysregulations of miRNA has been identified in many diseases including human cancer. However, only a few miRNAs associated with tamoxifen resistance has been reported. In this study, we found that lymphocyte antigen 6 complex (LY6K), which is a member of the Ly-6/μPAR superfamily and related to breast cancer progression and metastasis, is inversely correlated with ERα expression. We, for the first time, found miRNAs involved in the regulatory molecular mechanism between ERα and LY6K and related to tamoxifen susceptibility in breast cancer. miR-192-5p, induced by LY6K, downregulates ERα directly and induced tamoxifen resistance in ERα-positive breast cancer cells. In addition, re-expression of ERα in ERα-negative breast cancer cells increased miR-500a-3p expression and directly inhibits LY6K expression. Ectopic expression of miR-500a-3p sensitized ERα-negative cells to tamoxifen by increasing apoptosis. Finally, we observed an inverse correlation between LY6K and ERα in primary breast cancer samples. We found that patients with recurrence showed high expression of miR-192-5p after tamoxifen treatments. In addition, expression of miR-500a-3p was significantly correlated to survival outcome. As miRNAs involved in the regulatory mechanism between LY6K and ERα can affect tamoxifen resistance, downregulating miR-192-5p or re-expressing miR-500a-3p could be a potential therapeutic approach for treating tamoxifen resistant patients.

2024-08-01·Current Computer-Aided Drug Design

Synthesis and in-silico Studies of 4-phenyl thiazol-2-amine Derivatives as Putative Anti-breast Cancer Agents

Article

作者: Kaur, Kamalpreet ; Lavanya, Kanamarlapudi Joshna ; Jaitak, Vikas

Background::

Breast cancer (BC) is the second-leading cause of cancer-related fatalities in women after lung cancer worldwide. The development of BC is significantly influenced by estrogen receptors (ERs). The problem with current cancer treatments is selectivity, target specificity, cytotoxicity, and developing resistance. Thiazole scaffolds are gaining popularity in drug discovery due to their broad range of biological activity. It has the extraordinary capacity to control a variety of cellular pathways, and its potential for selective anticancer activity can be explored.

Objectives::

Synthesis and in-silico studies of 4-Phenyl thiazol-2-amine derivatives as anti-breast cancer agents and molecular docking was used to assess the compounds’ capacity to bind ER-α protein target.

Methods::

In this study, 4-Phenylthiazol-2-amine derivatives (3a-j) have been synthesized, and using Schrodinger software, molecular docking and ADME studies of the compounds were conducted.

Results::

Most of the synthesized compounds have shown dock scores ranging from -6.658 to - 8.911 kcal/mol, which is better than the standard drug tamoxifen (-6.821 kcal/mol). According to molecular docking, all compounds fit in the protein’s active site and have the same hydrophobic pocket as the standard drug tamoxifen. Further, all of the compounds’ ADME properties are below acceptable limits.

Conclusion::

Compound 3e showed the best docking score of -8.911. All compounds’ ADME properties are within acceptable limits, and their p/o coefficients fall within a range, suggesting they will all have sufficient absorption at the site of action. These compounds can be evaluated invitro and in-vivo in the future.

2024-03-01·Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis

Weekly intraperitoneal steroid infusion to treat recurrent ascites in a patient with early stage of peritoneal dialysis–related encapsulating peritoneal sclerosis: A case report

Article

作者: Tian, Ya-Chung ; Chen, Huai-Liang ; Chen, Kuan-Hsing ; Hung, Cheng-Chieh

Encapsulating peritoneal sclerosis (EPS) is a rare and potentially fatal complication of long-term peritoneal dialysis (PD). EPS-induced large volume and recurrent ascites represents a challenging condition. We report a 51-year-old man with kidney failure treated with PD for 13 years who eventually developed early stage of EPS accompanied with poor intake and recurrent ascites. After management including discontinuing PD and switching to haemodialysis, as well as oral steroids and tamoxifen administration, the patient had refractory ascites. An intervention of weekly intraperitoneal steroid infusion with methylprednisolone was implemented for a year. Gradually, we observed a reduction in ascites drainage, an improvement of clinical symptoms and the patient’s nutritional status. The PD catheter was successfully removed as there was no recurrence of ascites. Intraperitoneal corticosteroid administration represents a new intervention for patients with early stage of EPS and recurrent ascites after PD cessation.

172

项与枸橼酸他莫昔芬相关的新闻（医药）

2024-04-18

·药精通Bio

类器官 + 组学：精准医疗与新药研发的天作之合（上）

深度聚焦类器官与3D培养论坛，OTC2024论坛合作详询：王晨 180 1628 8769本文主要内容提炼、整理自Anmi Jose、Pallavi Kulkarni等人近期发表于《Molecular Cancer》（IF = 37.3）的综述文章：Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine.癌症是一个全球性的公共卫生问题，据世界卫生组织统计数据，2022年全球新增癌症病例约2000万例，死亡约970万例，预计2050年全球新增癌症病例将超过3500万例。因此，迫切需要更新的药物靶点、改进高通量药物发现渠道的筛选模式以及更好的个性化治疗方案。在这方面，越来越多的研究利用了“泛组学（Pan-Omics）”技术，如基因组学、表观基因组学、转录组学、蛋白质组学、代谢组学和脂质组学等，以精确揭示疾病的病理生理学并确定新的药物靶点。为此，近十年来出现了许多用于新药发现的高通量筛选平台。以二维培养细胞系和异种移植小鼠模型为代表的传统方法各自具有模拟度低、成本高周期长等的局限性，因而人们开始转向支持体外条件下3D培养细胞的技术。此外，癌症治疗方面已逐渐过渡到个体化精准医疗，即根据患者独特的生物学特征确定治疗方法，最终推动适用于患者个体的最佳治疗方案。同时，既往多项研究表明，3D体外疾病模型与患者的组学图谱分析相结合，不仅可以确定有效的治疗策略，还能够深入剖析癌症发生发展及耐药性的根本机制，从而发现新靶点，改进癌症治疗的格局。新药研发成本不断增加的原因在于临床试验和监管要求的复杂性。此外，从实验室到临床的成功率较低，这通常是由于缺乏适当的、生理学相关的临床前筛选模型来提高成功率。在寻找新靶点的过程中，随着组学技术的出现，从基因、转录本、蛋白质、代谢物及其相互作用网络的层面对生物样本进行评估已成为可能。将组学技术与体外3D模型相结合，阐明癌症细胞基因型和表型之间的复杂联系，在高通量药物筛选和药物发现方面具有巨大潜力。▲图将患者来源的体外3D肿瘤模型和泛组学技术整合，以促进精准医疗与新药研发（Jose A, Kulkarni P et al. Mol Cancer. 2024）01基因组学与体外3D模型各种基因组学方法，如DNA Microarray、Sanger测序、二代测序（NGS）和第三代长读数测序（TGS），能够对目标基因组进行测序，以阐明体细胞和种系水平的个体间变化。例如，随着高通量测序技术的出现，癌症基因组图谱计划（TCGA）通过对33个癌症患者分组的20000多例原发性肿瘤与匹配的正常样本进行分子表征，产生了大量的基因组、表观基因组、转录组和蛋白质组数据，从而可以帮助鉴定癌症治疗的潜在靶点，促进了个性化医疗的变革和加速。有许多研究人员通过识别肿瘤生物标志物、基因表达谱、单核苷酸多态性检测、耐药性相关的基因及预测药物反应，报告了基因组学与体外3D肿瘤模型在药物发现和精准医疗中的整合。例如，一篇文献报道了在多柔比星、紫杉醇和他莫昔芬等抗癌药物处理后，使用DNA Microarray比较乳腺癌3D模型和2D单层培养物中的基因表达谱；相对于2D培养物，3D模型显示出对化疗药物的抵抗力增强，这表明3D模型重现了癌的细胞组分结构、表型异质性和细胞外基质（ECM）对药物转运的屏障，最终导致了模型的化疗耐药性（Horning JL, et al. Mol Pharm. 2008）。此外，利用NGS进行的基因组分析已被用于疾病亚型分类以及疾病模型与患者肿瘤数据的对比。很多研究使用全基因组测序（WGS）和全外显子组测序（WES）来鉴定肿瘤模型的突变情况，并确认该模型是否保持了来源组织亚型的分子特征。例如，美国Englander精准医学研究所利用子宫癌和结肠癌患者来源的肿瘤类器官生物样本库，将WES与类器官高通量药物筛选相结合，以确定个体患者最有效的治疗选择（Pauli C, et al. Cancer Discov. 2017）。又如，韩国蔚山大学的研究人员将基因组学技术和组学数据库应用于结直肠癌类器官（CCO）队列，确定了影响肿瘤免疫微环境（TIME）的内在免疫基因组特征的重要性；CCO不仅再现了原发肿瘤的遗传特征，还发现了结直肠癌高度增殖和间质表型的两个不同的内在分子亚群；作者还发现TIME表型与微卫星不稳定性、Wnt/β-catenin信号传导通路和APC/KRAS基因突变有关，从而证明了肿瘤类器官可用于开发新的免疫学策略，对患者进行精确分层（Cho EJ, Kim M, et al. J Exp Clin Cancer Res. 2021）。因此，基于体外3D肿瘤模型的生物活库不仅能为临床试验的后续评估提供新的治疗方案，还能为处于新辅助治疗、辅助治疗、姑息治疗等阶段的患者提供新的治疗方案，从而进一步指导治疗方案选择有限的个体患者的临床决策。在经过验证的体外3D肿瘤模型和基因组测序方法的帮助下，还有可能确定导致药物敏感性和治疗响应的特定基因组驱动因素。有一项研究培养了胰腺癌患者来源的类器官，模拟了原发肿瘤的基因突变谱、转录谱亚型、治疗响应与患者预后，从而实现了前瞻性的治疗选择（Tiriac H, et al. Cancer Discov. 2018）。另一项研究构建了一个先进的、基于类器官的平台，用于CRISPR-Cas9 筛选，以进行高通量基因检测和肿瘤驱动因子的功能鉴定（Michels BE, et al. Cell Stem Cell. 2020）。体外3D肿瘤模型与NGS相结合的另一个令人兴奋的应用是协助临床医生识别适合靶向治疗的患者，以做出最优决策。例如，针对BRCA1和/或BRCA2基因突变，目前有几种基于NGS的伴随诊断（CDx）方法被用于鉴定适用聚ADP核糖聚合酶抑制剂（PARPi）疗法的患者；实际上，患者来源的体外3D肿瘤模型也可以被用作临床肿瘤学常规功能检测的一部分，评估PARPi的敏感性，并发现新的生物标记物来预测患者的临床结果。此外，一项前瞻性研究也提出，暴露于X射线的肿瘤类器官可用于评估同源重组能力，并鉴定可能受益于PARPi治疗的患者（Morice PM, et al. Br J Cancer. 2021）。总之，测序工具在基因组分析、确定药物敏感性基因组标记物、帮助医生做出适当的临床决策以改善患者治疗与护理等方面都显示出了潜力。02转录组学与体外3D模型转录组学的研究主要由以检测mRNA为代表的RNA测序（RNA-seq）驱动，通过将各种体外/体内模型与患者肿瘤组织进行比较来验证这些模型，在基因组学层面无法辨别的变化可能会在转录组学水平显现出来。因此，为了开发出更可靠的治疗方法，如果这些改变具有重要的病理意义，就应该对其进行检测。有许多研究报告了对PDO的转录组分析，以了解肿瘤的异质性、耐药性并预测其对药物的反应，有助于从机制上了解肿瘤的病理生理学特征。转录组学的进步促使单细胞转录组学（单细胞转录组测序，scRNA-seq）应用于精准医疗，scRNA-seq可以探索肿瘤微环境中存在的细胞多样性，解析复杂的异质性恶性组织中细胞-细胞间相互作用；scRNA-seq与体外3D肿瘤模型的结合解决了样本量和通量的限制。例如，一项研究将3D培养物与scRNA-Seq结合起来，分析了胰腺导管腺癌的病理生理学，用于药物筛选和发现（Jeong YJ, et al. J Clin Invest. 2023）；另一项研究利用实验室制备的胶质母细胞瘤类器官，为有效治疗方法的发现开辟了潜在的途径（Wang C, et al. NPJ Precis Oncol. 2024）。这种高通量测序系统不仅可以推断潜在的药物靶标，而且对于解释药物响应也很有相当大的价值。除了mRNA之外，microRNA（miRNA）在人类肿瘤细胞中也普遍存在失调现象，并在调控各种基因方面发挥着关键作用。尤其是细胞分泌出的外泌体中可能含有大量的miRNA，其能够有效介导癌细胞与正常细胞之间的交流，从而促进癌症的进展和转移。例如，一项研究对结直肠癌类器官与结直肠腺瘤类器官的miRNA图谱进行了全面分析，发现外泌体miRNA特征在癌与腺瘤的类器官中表达相异（Nagai H, et al. Digestion. 2021）。总之，体外3D肿瘤模型的转录组分析不仅在识别分子亚型、肿瘤异质性和耐药性方面具有巨大潜力，而且还能预测患者对药物的反应，从而指导适当的临床决策。03蛋白质组学与体外3D模型在一定的预设条件下，对细胞、组织或生物体中存在的所有蛋白质的研究被称为蛋白质组学。样品中未知蛋白质的鉴定依赖于三项基本技术：复杂蛋白质或肽混合物的分级分离、质谱（MS）、以及处理组合质谱数据的生物信息学方法。因此，利用蛋白质组学技术可以对样品中的多种蛋白质进行定量和定性分析。不过，基于高通量药物筛选的蛋白质组学应用，以及利用类器官等体外3D肿瘤模型评估疗效的方法，在很大程度上尚未得到探索。尽管如此，也有研究报道了对胰腺类器官胞外囊泡的蛋白质组学和功能蛋白质网络分析，揭示了正常胰腺和胰腺癌类器官的囊泡蛋白质分别参与了细胞稳态和囊泡运输机制；还发现了促肿瘤的标记物LAMA5、SDCBP和TENA在胰腺癌类器官的囊泡中上调，从而证明了它们作为早期疾病诊断或疾病和治疗监测生物标记物的潜力（Buenafe AC, et al. Sci Rep. 2022）。由于蛋白质组是细胞的主要功能成分，决定着细胞之间的交流方式，因此在疾病的发生和发展中起着重要作用。然而，要充分发掘蛋白质组学与体外3D疾病模型在药物发现方面的潜力，还需要利用更前沿的蛋白质组学技术（如基于质谱仪的单细胞蛋白质组学和空间蛋白质组学）开展进一步的研究。04代谢组学与体外3D模型包括质谱和核磁共振（NMR）光谱在内的代谢组学技术已广泛应用于体外3D肿瘤模型，以检测和量化肿瘤不同部位和不同微环境条件下的代谢物，对其进行表征、代谢组学分析和治疗靶点的鉴定；体外3D肿瘤模型与代谢组学的结合也被用于阐明疾病的进展过程。例如，一项研究发现，在器官型3D组织的培养中，增殖活跃的乳腺细胞和静止的乳腺细胞之间的代谢组变化主要基于三羧酸循环、氨基酸代谢和谷氨酰胺；此外还发现，快速增殖的细胞通过促进非必需氨基酸的产生和谷氨酰胺的合成代谢，参与碳和氮的合成代谢（Coloff JL, et al. Cell Metab. 2016）。这些发现突出了代谢组学在癌症研究中的重要性，并强调了代谢组学的变化对确定活跃增殖的癌细胞的复杂机制至关重要，尤其是在体外3D肿瘤模型的帮助下。同时，代谢组学分析有助于治疗靶点的确定。例如，有一研究利用3D肝脏和肿瘤组织共培养的集成仿生阵列芯片评价药物间相互作用和代谢诱导的抗癌生物活性，从而为药物开发提供支持（Neef SK et al. Metabolites. 2020）。总之，将高通量组学技术与体外3D肿瘤模型相结合，可以深入了解癌细胞及其周围环境的代谢变化，并将研究结果转化为个性化癌症疗法的发现和开发。05脂质组学与体外3D模型在实体瘤中，癌细胞会改变其脂肪酸代谢，以适应缺氧和代谢压力等受损的肿瘤环境，而这与不良的预后有关。因此，脂质组学是对于关键致瘤机制及药物治疗策略制定相关的脂质种类进行检测的重要技术。当前，脂质组学在体外3D肿瘤模型上的应用还比较少，但已有研究报道利用气相色谱质谱法确定了2D和3D模型中不同脂质代谢对耐药性的影响，结果表明硬脂酰辅酶A去饱和酶1（SCD-1）的表达与BRAF突变黑色素瘤的进展之间存在显著相关性；此外，与2D培养物相比，3D培养物对BRAF抑制剂表现出更强的抵抗力（Pisanu ME, et al. J Exp Clin Cancer Res. 2018）。另一项研究报道了腹水参与卵巢癌细胞代谢和转移的情况，酸性环境抑制了卵巢癌3D模型的生长，而碱性腹水环境则支持卵巢癌的进展，同时发现脂质代谢物与腹膜pH值有关；因此脂质代谢物、细胞因子、趋化因子和物理化学特征有助于对具恶性腹水的卵巢癌患者进行分层（Yang Q, et al. J Transl Med. 2022）。总之，类似的这些研究结果支持这样一个概念，即与2D模型相比，体外3D肿瘤模型可以更精确地复制体内的脂质微环境，并可在组学技术的帮助下用于研究脂质特征的改变在癌症中的作用。06表观遗传组学与体外3D模型组学技术还可用于研究表观遗传学，以了解表观遗传层面的变化如何影响癌症的发生和发展。染色质免疫共沉淀结合DNA测序（ChIP-seq）、甲基化DNA免疫共沉淀结合测序（MeDIP-seq）、利用转座酶的染色质可及性测序（ATAC-seq）等技术，是用于研究表观遗传修饰效应的各种表观组学技术，在肿瘤研究中已得到广泛应用。例如，有一项研究利用体内、体外3D模型对前列腺癌进行了综合解析，重点研究了致癌转录因子N-Myc；ChIP-seq与RNA-seq数据显示，N-Myc顺式调控组、转录组和组蛋白甲基化发生了显著的雄激素依赖性改变，这证实了N-Myc在前列腺癌上皮细胞转录组和表观基因组重编程中的作用（Berger A, et al. J Clin Invest. 2019）。为了探究结直肠癌对奥沙利铂药物处理的反应，另一项研究使用ATAC-Seq与RNA-Seq对结直肠癌3D肿瘤模型进行了染色质可及性和转录组的综合分析，发现奥沙利铂处理后，28个基因的染色质开放发生了显著变化，阐明了在奥沙利铂耐药性中起关键作用的基因的染色质可及性变化机制（Tung KL, et al. Genes Dis. 2019）。总之，在能够高度模拟体内状况的体外3D肿瘤模型中，结合用药处理等干预措施与表观遗传组学技术，可以解释相关干预措施下肿瘤细胞中表观遗传图景的变化，从而探索更为广泛的分子机制、更深入的药物靶点。总而言之，以类器官为代表的体外3D肿瘤模型通过忠实模拟来源肿瘤组织的基因型、表型、空间结构、与细胞外基质间的相互作用等特征，提供了一个前景广阔、与临床相关的药物筛选/发现平台。将泛组学技术与这些3D肿瘤模型相结合，可以揭示肿瘤发生、进展、转移、耐药性等方面的详细机制，从而促进其转化应用。总结上海万何圆生物科技有限公司（Shanghai OneTar Biomedicine）始终坚持以客户为中心、以最前沿的类器官技术为核心，致力于打造“类器官+”的精准医疗、新药研发及转化医学平台。在临床精准医疗服务方面，万何圆推出万何康®类器官药敏检测平台，可将肿瘤类器官药敏检测与NGS检测结合，为患者提供更加精准的用药指导，能够为患者提供从个性化药敏检测方案制定、临床用药方案推荐、循证学依据展示到报告解读的一系列完善解决方案。在科研服务方面，万何圆推出类器官+单细胞测序双平台，可通过对类器官相关的干预性实验结合单细胞转录组测序技术，深入解析肿瘤异质性、生态位调控、细胞间通讯、耐药性等机制，双倍赋能研究成果，助力高分文章发表。参考文献Jose A, Kulkarni P, et al. Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine. Mol Cancer. 2024;23(1):50.END深度聚焦类器官与3D培养论坛，OTC2024论坛合作详询：王晨 180 1628 8769戳“阅读原文”立即领取限量免费参会名额!

临床研究

2024-04-12

·Healthcare Digital

AstraZeneca Company Profile, as CEO Soriot Lands pay Deal

An aerial shot of the AstraZeneca HQ in Cambridge, England. As it's announced AstraZeneca's CEO Pascal Soriot's package could rise by as much as US$24mn we explore the history of the UK's most valuable business AstraZeneca is the biggest UK-based business, with a market capitalisation of US$228bn. This week the Anglo-Swedish company approved a pay policy that will see CEO Pascal Soriot's package rise by as much as US$24mn. This will take his maximum annual bonus for 2024 to three times his base salary, and make him eligible for long-term performance-based share awards worth as much as 8.5 times his salary. It makes Soriot one of the best-paid executives among London's blue-chip FTSE 100 companies. AstraZeneca says the pay policy changes are necessary to increase competitiveness against its European peers and to “recognise leadership's critical role in achieving its long-term targets”. In the wake of the pay deal, we take a look at AstraZeneca – its history and some of the medical milestones it has achieved in that time. The history of AstraZeneca AstraZeneca, was founded in 1999, through the merger of Astra AB and Zeneca Group. Astra AB was a Swedish pharmaceutical company that was founded in 1913 by pharmacist Gustaf Dyrssen. Initially it produced dental and veterinary products, but later shifted focus to pharmaceuticals. In the 1950s, Astra expanded globally, entering the US market in the 1980s. Among its most important medicines were Nexium (esomeprazole), a proton-pump inhibitor used to treat gastroesophageal reflux disease and peptic ulcers, and Symbicort (budesonide/formoterol), a combination inhaler used to manage asthma and chronic obstructive pulmonary disease. Zeneca Group was established in 1993 through the demerger of Imperial Chemical Industries (ICI), which was focused on pharmaceuticals, agrochemicals and specialty chemicals. Its roots go back to 1923, when ICI formed its pharmaceutical division, and Zeneca grew through a series of acquisitions and research breakthroughs – notably cancer treatments including tamoxifen, used in the treatment of hormone receptor-positive breast cancer, and Casodex (bicalutamide), used to treat prostate cancer. The merger between Astra AB and Zeneca The $33bn merger between the two companies in 1999 was a strategic move to create a stronger global presence and to bolster research and development capabilities. Astra's expertise in cardiovascular and gastrointestinal drugs was complemented by Zeneca's strengths in oncology and respiratory medicines, and the merger has seen AstraZeneca go on to become a leader in innovative healthcare solutions. Some of AstraZeneca’s landmark treatments since 1999 ‘Blockbuster drugs Crestor (rosuvastatin) for cholesterol management, Seroquel (quetiapine) for schizophrenia and bipolar disorder and Nexium (esomeprazole) for acid reflux. Important lung cancer treatments, such as Iressa (gefitinib), Faslodex (fulvestrant) and Tagrisso (osimertinib). Extensive R&D in areas such as cardiovascular diseases, respiratory conditions and oncology. The Oxford-AstraZeneca COVID-19 vaccine One of AstraZeneca’s most notable medical achievement was partnering with the University of Oxford to develop a COVID-19 vaccine known as AZD1222, or the Oxford-AstraZeneca vaccine. The company’s role in this was pivotal, and included funding, manufacturing and distributing the vaccine. It also played a key role in conducting clinical trials, obtaining regulatory approvals, and scaling up production to meet global demand. The vaccine was based on a viral vector platform, a technique that uses a modified virus – or vector virus – as a treatment delivery mechanism. The Oxford-AstraZeneca vaccine was approved for emergency use in January 2021, shortly after approval was received by the Pfizer-BioNTech and Moderna vaccines (both December 2020). AstraZeneca provided the vaccine on a not-for-profit basis during the pandemic, and collaborated with various organisations to ensure equitable access to vaccines globally.

上市批准并购疫苗

2024-04-04

·BioSpace

Medigene AG Secures European Patent for its iM-TCR Technology

Planegg/Martinsried, April 4, 2024. Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, today announced that the Company has been issued a patent by the European Patent Office protecting its inducible Medigene T cell receptor (iM-TCR) technology, which contains a control mechanism to regulate efficacy and improve safety of its T cell receptor engineered T cell (TCR-T) therapies. “Over the past years we have conscientiously built an extensive international intellectual property portfolio across major markets, which we expect will provide a significant competitive advantage. Each technology we design and develop aims to enhance efficacy and mitigate safety risk to the patient and is based on our extensive immunology research and experience. We are pleased to receive this latest patent grant for our iM-TCR technology from the European Patent Office, which complements our recently granted patent in Japan,” said Dolores Schendel, CSO at Medigene. “At the core of our comprehensive expertise in T cell immunology, specifically TCR-based therapies, is our ability to generate optimal TCRs. Our decades of research and development is manifested in our innovative, proprietary End-to-End Platform technologies, such as the iM-TCR that has the potential to optimize safety and efficacy of TCR-T therapies for patients.” TCR-T therapies have demonstrated that they can effectively kill tumor cells. However, excessive activation of T cells may lead to premature exhaustion or cell death, as well as unwanted overactivity and the potential development of inflammatory responses in the body. The iM-TCR technology modifies the TCR to achieve control of TCR surface expression, allowing for fine-tuning of activity against tumor cells and thereby reducing potential inflammatory responses in the body. This property is of potential benefit not only to our current autologous TCR-T therapy assets, but potentially also applicable to other TCR-T based modalities. Additionally, the iM-TCR technology can potentially expand the range of targets and indications of vital or more sensitive tissue origin and provide additional safety when expanding to other disease areas beyond oncology. --- end of press release --- About Medigene AG Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing differentiated T cell therapies for treatment of solid tumors. Its End-to-End Platform is built on multiple proprietary and exclusive technologies that enable the Company to generate optimal T cell receptors against both cancer testis antigens and neoantigens, armor and enhance these T cell receptor engineered (TCR) -T cells to create best-in-class, differentiated TCR-T therapies, and optimize the drug product composition for safety, efficacy and durability. The End-to-End Platform provides product candidates for both its own therapeutics pipeline and partnering. Medigene’s lead TCR-T program MDG1015 is expected to receive IND/CTA approval in the second half of 2024. For more information, please visit About Medigene’s inducible TCR (iM-TCR) The T cell receptor (TCR) assembly is a complex process. In humans, TCRs consist of an alpha (α) chain and a beta (β) chain and each chain possesses a constant and a variable part. Medigene´s proprietary iM-TCR technology prevents the normal pairing of the α and the β chains by introduction of specific engineered sequences into the constant part of each TCR chain. Each engineered chain is linked to an estrogen receptor sequence, which only allows the two iM-TCR chains to pair (dimerize) in the presence of Tamoxifen, and be expressed and function at the surface of TCR-T cells in a normal manner. Consequentially, to enable the iM-TCR-T cells to function in tumor cell recognition and killing, Tamoxifen administration is required but the levels required for dimerization and TCR-T function are orders of magnitude lower than the commonly used therapeutic doses. Any TCR from Medigene’s broad library of 3S TCRs can be equipped with the proprietary iM-TCR technology, which enables the function of tumor-specific TCR-T cell therapies to be finely tuned for safety and efficacy according to clinical needs. For more information on our iM-TCR technology, please visit About Medigene’s End-to-End Platform Medigene’s immunotherapies help activate the patient’s own defense mechanisms by harnessing T cells in the battle against cancer. Medigene’s End-to-End Platform combines multiple exclusive and proprietary technologies to create best-in-class, differentiated TCR-T therapies. The platform includes multiple TCR generation and optimization technologies (e.g., Allogeneic-HLA (Allo-HLA) TCR Priming), as well as product enhancement technologies (e.g., PD1-41BB and CD40L-CD28 costimulatory switch proteins, iM-TCR) to address challenges in developing effective, durable and safe TCR-T therapies. Partnerships with multiple companies including BioNTech and Regeneron, continue to validate the platform’s assets and technologies. This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only. Medigene AG Pamela Keck Phone: +49 89 2000 3333 01 Email: investor@medigene.com In case you no longer wish to receive any information about Medigene, please inform us by e-mail (investor@medigene.com). We will then delete your address from our distribution list.

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研发状态

适应症	最高研发状态	国家/地区	公司
乳腺癌	批准上市	日本更多	AstraZeneca KK 更多
非浸润性导管内癌	批准上市	美国更多	Mayne Pharma, Inc. 更多
膀胱癌	无进展	美国更多	AstraZeneca PLC 更多
痴呆	无进展	意大利更多	AstraZeneca PLC 更多
尿路上皮癌	无进展	意大利更多	AstraZeneca PLC 更多

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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


NCT00295646 (CTgov)	临床3期	HR阳性乳腺癌	1,803	goserelin+zoledronic acid+anastrozole (AZ (Arimidex+Zoledronate))	築顧醖壓願鹹糧顧鹽夢(製艱窪簾壓齋蓋繭憲鹹) = 製範築鑰範選醖壓鑰憲願鬱艱鏇餘鏇鏇鹽製範 (網範積艱衊窪簾製願觸, 餘觸醖齋遞膚獵構鏇艱 ~ 鹽鬱製壓廠鑰遞獵積繭) 更多	-	2024-03-15
				goserelin+Tamoxifen+zoledronic acid (TZ (Tamoxifen+Zoledronate))	築顧醖壓願鹹糧顧鹽夢(製艱窪簾壓齋蓋繭憲鹹) = 壓觸繭淵積齋選醖夢選願鬱艱鏇餘鏇鏇鹽製範 (網範積艱衊窪簾製願觸, 網遞觸壓製憲蓋窪夢獵 ~ 鏇選觸築憲艱膚淵鹹鏇) 更多
NCT01674140 (CTgov)	临床3期	HR阳性/HER2阴性乳腺癌	1,939	placebo+letrozole+tamoxifen citrate+exemestane+leuprolide acetate+goserelin acetate+anastrozole (Placebo)	壓鹹願壓願鏇夢糧糧憲(顧蓋鹹選齋願積選獵築) = 積鑰齋醖觸餘獵築鏇壓網憲衊憲構襯鬱糧簾餘 (鬱範獵衊觸繭鏇淵糧淵, 鑰獵製製憲憲鹹夢艱鬱 ~ 鏇艱壓繭願壓壓鬱網繭) 更多	-	2023-12-20
				Everolimus (Everolimus)	壓鹹願壓願鏇夢糧糧憲(顧蓋鹹選齋願積選獵築) = 廠築壓選製積願築鑰醖網憲衊憲構襯鬱糧簾餘 (鬱範獵衊觸繭鏇淵糧淵, 襯獵構壓夢鑰膚顧觸製 ~ 鹹壓願願簾憲糧憲窪餘) 更多
AASLD2023	N/A	乳腺癌	233	No hormone therapy	蓋襯願鑰築艱鏇鑰膚憲(積蓋範鹽鹹願壓遞築襯) = 網鏇夢鏇獵遞構鹽憲製衊膚願顧壓選築範廠構 (積窪窪網鬱繭遞範憲鏇 ) 更多	-	2023-11-10
				Anastrozole	蓋襯願鑰築艱鏇鑰膚憲(積蓋範鹽鹹願壓遞築襯) = 獵鏇網製餘觸網壓簾夢衊膚願顧壓選築範廠構 (積窪窪網鬱繭遞範憲鏇 ) 更多
NCT03870399 (HORMONET, Pubmed)	临床2期	神经内分泌肿瘤	23	Tamoxifen	繭製糧窪膚憲糧廠願餘(鏇窪齋齋鬱艱鏇醖積齋) = 獵繭膚鹽遞簾餘積鬱廠醖願網蓋範鬱遞鑰鹽衊 (鹽鑰簾鏇膚構淵艱窪顧 ) 更多	-	2023-01-01
TOTAM study (EBCC2022)	N/A	乳腺癌辅助 endoxifen levels	20	Tamoxifen dose reduction	願襯夢選艱夢窪願淵夢(製簾觸壓鹹窪獵膚鹹壓) = 壓醖簾憲蓋膚壓繭簾構壓壓壓夢鹽蓋壓鬱觸鹹 (網顧醖衊鑰構構醖築繭 ) 更多	-	2022-11-17
ESGO2022	N/A	子宫内膜癌 estrogen receptor \| progesterone receptors	83	Tamoxifen-progestin combination therapy	獵夢餘鹽鹹醖衊糧膚願(鹹鹽鏇淵鹹製選夢窪網) = 鹽廠鬱蓋鑰獵簾鹽餘繭鹽壓鏇夢觸醖築製鏇積 (鹽鬱遞繭繭壓糧繭積襯 )	积极	2022-10-20
				Progestin-only therapy	獵夢餘鹽鹹醖衊糧膚願(鹹鹽鏇淵鹹製選夢窪網) = 鑰齋淵簾願鹹蓋襯範觸鹽壓鏇夢觸醖築製鏇積 (鹽鬱遞繭繭壓糧繭積襯 )
NCT03870399 (HORMONET, ESMO2022)	临床2期	神经内分泌肿瘤	23	Tamoxifen 20mg	遞觸觸餘窪遞醖膚鏇選(襯選壓鹹衊艱鑰鬱窪積) = 淵鏇襯鬱夢淵簾網襯積範鹽選齋遞壓願廠願壓 (獵膚膚鑰築膚蓋製蓋網 )	-	2022-09-10
PHIX-IT (ISTH2022)	N/A	乳腺癌	-	Edoxaban without tamoxifen	顧醖膚鹽蓋築積齋鏇衊(廠醖獵襯艱夢糧鬱繭夢) = 鏇鏇廠遞顧鬱選窪鏇顧壓壓鏇醖餘鹽製襯範淵 (鑰憲構鏇夢蓋鑰範網繭 )	积极	2022-07-09
				Edoxaban with tamoxifen	顧醖膚鹽蓋築積齋鏇衊(廠醖獵襯艱夢糧鬱繭夢) = 夢廠憲夢膚壓鹽憲鹹選壓壓鏇醖餘鹽製襯範淵 (鑰憲構鏇夢蓋鑰範網繭 )
ASCO2022	N/A	乳腺癌辅助	1,235	Tamoxifen	製願廠顧製醖鏇獵繭衊(製憲憲醖艱鹽觸製壓製) = 築醖選積襯膚鹹顧顧淵蓋製艱製艱膚廠製齋構 (鹹蓋選積鬱築遞憲製顧, 80 ~ 125)	-	2022-06-02
ASTRRA (ASCO2022)	N/A	乳腺癌	-	Tamoxifen only	餘廠窪鑰壓選鏇淵鬱蓋(簾獵簾膚膚選願淵積衊) = 壓範製選鏇築餘遞範膚願遞簾憲蓋繭艱鑰鏇製 (願窪願觸醖製憲糧鹽積 ) 更多	积极	2022-06-02
				Tamoxifen + Ovarian function suppression	餘廠窪鑰壓選鏇淵鬱蓋(簾獵簾膚膚選願淵積衊) = 築廠鹹願範築鏇艱鹹選願遞簾憲蓋繭艱鑰鏇製 (願窪願觸醖製憲糧鹽積 ) 更多