更新于：2024-05-01

SSTR2

生长抑素受体2

更新于：2024-05-01

基本信息

别名

somatostatin receptor 2、Somatostatin receptor type 2、SRIF-1

+ [5]

简介

Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization.

关联

项与 SSTR2 相关的药物

Lutetium Dotatate LU-177

(177镥)镥氧奥曲肽

靶点

SSTR2

作用机制

SSTR2拮抗剂 [+1]

在研机构

FUJIFILM Toyama Chemical Co. Ltd. [+10]

原研机构

Advanced Accelerator Applications SA

在研适应症

神经内分泌肿瘤 [+22]

非在研适应症

大肠类癌 [+1]

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2017-09-26

Pasireotide Diaspartate

门冬氨酸帕瑞肽

靶点

SSTR1 x SSTR2 x SSTR3 x SSTR5

作用机制

SSTR1激动剂 [+3]

在研机构

Recordati Rare Diseases, Inc. [+5]

原研机构

Novartis Pharma AG

在研适应症

生长激素过多 [+6]

非在研适应症

腺瘤 [+36]

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2012-04-24

Vapreotide Acetate

醋酸伐普肽

靶点

SSTR2 x SSTR5

作用机制

SSTR2诱导剂 [+1]

在研机构

Debiovision, Inc.

原研机构

Debiopharm International SA

在研适应症

食管胃静脉曲张

非在研适应症

食道静脉瘤出血

最高研发阶段批准上市

首次获批国家/地区

墨西哥

首次获批日期2007-06-18

298

项与 SSTR2 相关的临床试验

NCT06326190 / Not yet recruiting临床2期

177Lu-DOTATATE for Recurrent Meningioma: a Randomized Phase II Study

Novel treatments are urgently needed for meningiomas progressing after local therapies (surgery, radiotherapy). So far, no effective systemic therapies are known in this situation. The LUMEN-1 trial will investigate in a prospective randomized trial the efficacy of the precision medicine "theranostic" concept of combining diagnostic patient selection using PET-based molecular imaging and target-specific therapeutic intervention using a systemically administered radioligand.
The rationale for the LUMEN-1 trial is based on the following: (a) high somatostatin receptor (SSTR) expression in meningiomas, (b) wide-spread availability of clinically established SSTR-PET imaging, (c) proven efficacy of SSTR-targeting radioligand therapy using [177Lu]Lu-DOTATATE in another tumor type (neuroendocrine tumors), and (d) promising experiences with [177Lu]Lu-DOTATATE therapy in compassionate use applications and retrospective case series and interim results from one ongoing uncontrolled prospective trial in meningiomas. LUMEN-1 is the first randomized clinical trial to investigate [177Lu]Lu-DOTATATE therapy in refractory meningioma and may open new avenues for treatment and research in this area.

开始日期2024-11-06

申办/合作机构

EORTC

[+1]

NCT05687123 / Recruiting临床1期IIT

A Phase I Dose Escalation-Expansion Trial of Sunitinib Malate Plus Lutetium Lu 177 Dotatate (Lutathera) in Somatostatin Receptor Positive Pancreatic Neuroendocrine Tumors

This phase I trial tests the safety, side effects, and best dose of sunitinib malate in combination with lutetium Lu 177 dotatate in treating patients with pancreatic neuroendocrine tumors. Sunitinib malate is in a class of medications called kinase inhibitors and a form of targeted therapy that blocks the action of abnormal proteins called VEGFRs that signal tumor cells to multiply. This helps stop or slow the spread of tumor cells. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and not harm normal cells. It is also a form of targeted therapy because it works by attaching itself to specific molecules (receptors) on the surface of tumor cells, known as somatostatin receptors, so that radiation can be delivered directly to the tumor cells and kill them. Giving sunitinib malate and lutetium Lu 177 dotatate in combination may be safer and more effective in treating pancreatic neuroendocrine tumors than giving either drug alone.

开始日期2024-07-04

申办/合作机构

National Cancer Institute

NCT06379217 / Not yet recruiting临床1期

A Phase I, Open-label, Multi-center Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.

The purpose of this study is to evaluate the change in the expression of treatment targets on the surface of tumor cells (Prostate Specific Membrane Antigen (PSMA), Somatostatin Receptor 2 (SSTR2), and Gonadotropin Releasing Hormone Receptor (GRPR)) between the start and after the completion of radioligand therapy (RLT). Study will use radioligand imaging (RLI) to determine predominantly expressed target on the surface of tumor cells. Based on predominant expression of target, corresponding RLT targeting PSMA, SSTR2, or GRPR RLT will be given for up to 6 cycles every 6 weeks as intravenous (i.v.) injection in participants with metastatic neuroendocrine prostate cancer (mNEPC).

开始日期2024-06-18

申办/合作机构

Novartis Pharmaceuticals Corp.

100 项与 SSTR2 相关的临床结果

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100 项与 SSTR2 相关的转化医学

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0 项与 SSTR2 相关的专利（医药）

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1,662

项与 SSTR2 相关的文献（医药）

2024-02-23·Science advances

Identification of the metaphyseal skeletal stem cell building trabecular bone.

Article

作者: Guan Yang ; Qi He ; Xiaoxiao Guo ; Rong-Yu Li ; Jingting Lin ; Yiming Lang ; Wanyu Tao ; Wenjia Liu ; Huisang Lin ; Shilai Xing ; Yini Qi ; Zhongliang Xie ; Jing-Dong J Han ; Bin Zhou ; Yan Teng ; Xiao Yang

Skeletal stem cells (SSCs) that are capable of self-renewal and multipotent differentiation contribute to bone development and homeostasis. Several populations of SSCs at different skeletal sites have been reported. Here, we identify a metaphyseal SSC (mpSSC) population whose transcriptional landscape is distinct from other bone mesenchymal stromal cells (BMSCs). These mpSSCs are marked by Sstr2 or Pdgfrb⁺Kitl^-, located just underneath the growth plate, and exclusively derived from hypertrophic chondrocytes (HCs). These HC-derived mpSSCs have properties of self-renewal and multipotency in vitro and in vivo, producing most HC offspring postnatally. HC-specific deletion of Hgs, a component of the endosomal sorting complex required for transport, impairs the HC-to-mpSSC conversion and compromises trabecular bone formation. Thus, mpSSC is the major source of BMSCs and osteoblasts in bone marrow, supporting the postnatal trabecular bone formation.

2024-02-19·Scientific reports

Somatostatin receptor 2 (SSTR2) expression is associated with better clinical outcome and prognosis in rectal neuroendocrine tumors.

Article

作者: Joo Young Kim ; Jisup Kim ; Yong-Il Kim ; Dong-Hoon Yang ; Changhoon Yoo ; In Ja Park ; Baek-Yeol Ryoo ; Jin-Sook Ryu ; Seung-Mo Hong

Somatostatin analogues have recently been used as therapeutic targets for metastatic or surgically unresectable gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), and associated somatostatin receptor (SSTR) expression has been well demonstrated in most GEP NETs, with the exception of rectal NETs. SSTR2 immunohistochemical expressions were evaluated in 350 surgically or endoscopically resected rectal NETs and compared to clinicopathologic factors. SSTR2 expression was observed in 234 (66.9%) rectal NET cases and associated tumors with smaller size (p = 0.001), low pT classification (p = 0.030), low AJCC tumor stage (p = 0.012), and absence of chromogranin expression (p = 0.009). Patients with rectal NET and SSTR2 expression had significantly better overall survival than those without SSTR2 expression both by univariable (p = 0.006) and multivariable (p = 0.014) analyses. In summary, approximately two-thirds of rectal NETs expressed SSTR2. SSTR2 expression was significantly associated with favorable behavior and good overall survival in patients with rectal NETs. Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues.

2024-02-18·Chemphyschem : a European journal of chemical physics and physical chemistry

Uncovering Energetic Positions of Surface Trap States in α-Fe2O3 Treated with Cobalt Phosphate (Co-Pi) Using Charge Carrier-Selective Heterodyne Transient Grating Technique.

Article

作者: Young Hyun Kim ; Yu Gyeong Bae ; Woon Yong Sohn

Near-field heterodyne transient grating (NF-HD-TG) responses of hematite (α-Fe2O3) treated with cobalt phosphate (Co-Pi) were measured with the burn lasers inducing the depletion of the response by the removal of the trapped charge carriers in the target state, which is called charge carrier-selective heterodyne transient grating (CS-HD-TG) spectroscopic technique. We found that two distinct trap states co-existed in Co-Pi loaded on the surface of α-Fe2O3. One of them named r-SS2, of which potential was similar to that of r-SS1 in the surface of α-Fe2O3, acted as a recombination centre but could increase the lifetime of the trapped holes by the charge separation. We also revealed that the energetic position of the other (i-SS2), which has been regarded as the intermediate state for oxygen evolution reaction with low overpotential, was higher than that of i-SS1 in α-Fe2O3 but lower than those of r-SS1 and r-SS2.

项与 SSTR2 相关的新闻（医药）

2024-04-04

·PRNewswire

Ariceum Therapeutics to present new radioligand therapy data at American Association for Cancer Research (AACR) Annual Meeting 2024

BERLIN, April 4, 2024 /PRNewswire/ -- Ariceum Therapeutics (Ariceum), a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, today announces that it will be presenting a poster, demonstrating its new findings on the discovery of novel macrocyclic peptide radioligands for tumor therapy by mRNA display in collaboration with research partner, UCB, a global pharmaceutical company, at this year's American Association for Cancer Research (AACR) Annual Meeting, held 5-10 April 2024 in San Diego, California. The findings describe the selection and initial characterization of macrocyclic peptides against an undisclosed target discovered using UCB's mRNA-display technology platform, ExtremeDiversity™. Macrocyclic peptides are potent ligands for radioligand therapeutics (RLT) that aim to selectively deliver radioisotopes to cancer tissues to eradicate tumor cells while limiting the damage to surrounding tissues. This new data highlights the potential of UCB's mRNA display platform for fast and efficient discovery of highly specific macrocyclic peptides with optimal binding properties suitable for RLT. Manfred Rüdiger, Chief Executive Officer at Ariceum Therapeutics, said: "Following our exclusive, strategic research collaboration with UCB, we look forward to presenting new findings related to the identification of highly specific macrocyclic peptides for use in radioligand therapeutics at this year's AACR Annual Meeting. These data have positive implications for the future development of RLT and are a potential game-changer in precision cancer therapy. AACR's Annual Meeting is the perfect industry forum at the forefront of cancer research at which to present our findings." Details of the poster presentation are as follow: Title: Discovery of novel macrocyclic peptide radioligands for tumor therapy by mRNA display Presenting Author: Anika Jaekel, Senior Director, Head of Translational Biology and Non-Clinical Pharmacology at Ariceum Therapeutics Session Category: Experimental and Molecular Therapeutics Session Title: Radiation, Theranostics, Radiotheranostics, Normal Tissue, and Cellular Stress Session Date and Time: Tuesday 9 April 2024, 1:30 PM - 5:00 PM PDT Location: Poster Section 29 Poster Board Number: 7 Abstract Number: 6025 Abstracts are available in an online itinerary planner here and will be available in on online only supplement to the AACR journal Cancer Research one month after the conference. Notes to Editors About Ariceum Therapeutics Ariceum Therapeutics (Ariceum) is a private, clinical stage radiopharmaceutical company focused on the diagnosis and precision treatment of certain neuroendocrine and other aggressive, hard-to-treat cancers. The name Ariceum is an anagram of 'Marie Curie' whose discovery of radium and polonium have been huge contributions to finding treatments for cancer. Ariceum's lead targeted systemic radiopharmaceutical product, 177Lu-satoreotide tetraxetan ("Satoreotide"), is an antagonist of the somatostatin type 2 (SSTR2) receptor which is overexpressed in neuroendocrine tumours (NETs) and some aggressive cancers such as small cell lung cancer (SCLC), or Merkel Cell Carcinoma, all of which have few treatment options and poor prognosis. Satoreotide is being developed as a 'theranostic' pair for the combined diagnosis and targeted radionuclide treatment of these tumours. Ariceum is also developing a radiolabelled PARP-inhibitor (ATT001), which is slated to enter clinical development in 2024. ATT001 was part of the acquisition of Theragnostics Ltd which was closed in June 2023. Ariceum Therapeutics, launched in 2021, acquired all rights to Satoreotide from Ipsen. Ipsen remains a shareholder in the Company. Ariceum is headquartered in Berlin, with operations in Germany, Switzerland, Australia, United Kingdom and United States of America and with activities currently across the globe. Ariceum is led by a highly experienced management team and supported by specialist investors including EQT Life Sciences (formerly LSP), HealthCap, Pureos Bioventures, Andera Partners and Earlybird Venture Capital. For further information, please visit . About AACR Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 54,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 130 countries and territories around the world. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting. For more information about the AACR, visit AACR.org. SOURCE Ariceum Therapeutics

并购AACR会议寡核苷酸

2024-03-23

·医药魔方

临研速递 | 免疫组合疗法的成功与失利（CheckMate-9DW和KEYLYNK-006关键结果）

随着生物科学技术的进步，各种类型创新疗法不断涌现并在临床研究得到验证，展现出了巨大的临床潜力。新技术、新靶点药物的早期临床研究与注册性临床研究（Pivotal Trial）的价值在整个药物研发中日益显著。其中，试验结果对于适应症拓展与后续研究的方案制定具有举足轻重的作用，因而对结果的解读很有必要。医药魔方NextPharma & TrialCube数据库围绕行业现状及未来趋势，将早期临床研究与注册性临床研究的结果进行筛选，并对其中关键结果进行可视化呈现，以期赋能医药伙伴（可于文章后免费申请数据库试用）。医药魔方数据库现建立“临研速递”专栏，定期发布精选的早期临床研究与注册性临床研究的可视化结果，敬请期待。本期筛选的三项注册性临床研究分别是 PATHFNDR-2、CheckMate-9DW和KEYLYNK-006 ，可视化结果如下。注册性临床研究 ▌PATHFNDR-2(NCT05192382)推荐理由：paltusotine治疗肢端肥大症的III期注册性临试验PATHFNDR-2研究结果积极，治疗24周有56%的受试者达到主要终点，安慰剂组仅为5%。paltusotine作为一款靶向SSTR2小分子激动剂，其在肢端肥大症上取得成功，有望为该类人群带来新的治疗选择。▌CheckMate-9DW(NCT04039607)推荐理由：O+Y双免疗法一线治疗晚期肝细胞癌的III期注册性临试验CheckMate-9DW研究结果积极，相较于索拉非尼或仑伐替尼，双免联合疗法组患者总生存期显示出统计学意义和临床意义的改善。O+Y双免疗法在晚期一线HCC患者群体中取得突破，有望为此类患者带来新选择。▌KEYLYNK-006(NCT03976323)推荐理由：K药+奥拉帕利联合疗法一线治疗转移性非鳞状非小细胞肺癌的III期注册性临试验KEYLYNK-006研究未达到OS和PFS的双主要终点。K药+奥拉帕利联合疗法组合再次失利，此前在一线鳞状非小细胞肺癌上也未获成功。此组合在非小细胞肺癌上的探索充满坎坷。▌NextPharma & TrialCube如何获得？免费申请试用方式如下：1、扫描下方二维码2、点左下方“阅读原文”，直接跳转申请链接Copyright © 2024 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

临床结果临床3期免疫疗法临床2期

2024-03-20

·佰傲谷BioValley

大厂们纷纷下注放射性偶联药物

2024年3月19日，阿斯利康（AstraZeneca）宣布已经达成最终协议，对Fusion Pharmaceuticals进行收购。Fusion是一家开发放射性偶联药物的临床阶段生物制药公司。根据协议，阿斯利康以每股21美元的现金收购Fusion公司的所有流通股，总交易价值约为20亿美元，此次收购价格大约在Fusion公司周一收盘价上溢价97%。此外，阿斯利康还增加了每股价值3美元的或有价值权CVR，在达到里程碑后付款，这使得交易金额达到24亿美元。据报道，这笔交易将于2024年第二季度完成。交易完成后，Fusion将作为阿斯利康的全资子公司运营。阿斯利康将获得Fusion拥有的放射偶联药物管线，其中交易核心是FPI-2265；以及基于同位素锕225的放射偶联药物的专业知识和研发能力。阿斯利康的交易重点FPI-2265是一种基于锕225的PSMA靶向放射偶联药物，通过PSMA靶向小分子药物与锕225偶联，利用PSMA靶向药物精准靶向肿瘤组织，然后锕225释放α粒子对肿瘤细胞进行杀伤。同时，由于α粒子在组织中产生作用的距离很短，只有几个细胞的宽度，因此对附近正常健康组织的风险很小。FPI-2265主要被开发用于治疗转移性去势抵抗性前列腺癌（mCRPC），目前处于2期试验阶段。预计将于2024年第一季度报告初步数据。除了FPI-2265，Fusion还在利用其α同位素的专业知识开发了其他多款α放射免疫偶联药物管线，包括已经进入临床阶段的FPI-1434（IGF-1R抗体偶联锕225）和FPI-2059（NTSR1靶向分子偶联锕225）；以及与外部合作的管线。对于偶联物来说，连接子一直是比较令人关注的问题。根据Fusion公司官网介绍，Fusion拥有专有的Fast-Clear™连接子技术，能够促进不与癌细胞特异性结合的同位素快速排泄，从而扩大治疗窗口。目前，Fusion公司正在利用Fast-Clear™技术应用于一系列药物，包括小分子和抗体。放射性偶联药物成为热潮放射性偶联药物主要是通过将放射性核素附着在靶向剂上，实现对肿瘤的精准辐射，降低对正常组织的损伤。与其他类型的偶联药物最大的不同在于，RDC的有效载荷不再是毒性分子，而是放射性核素。相较于传统的放射疗法，放射性偶联药物能够实现特异性给药，能够提高潜在疗效，并且降低治疗副作用，减少对健康细胞的伤害。此外，由于放射性核素能够起到影像诊断的作用，相较于其他的偶联物，放射性偶联药物可以用于诊断性成像。延伸阅读：诺华RDC药物（放射性核素偶联物）Pluvicto获FDA批准上市随着美国FDA对诺华Lutathera （177Lu-dotatate）和Pluvicto（177Lu-PSMA-617）的批准，然后销售火爆——Lutathera的2023年总销售为6.05亿美元，Pluvicto为9.8亿美元，两者均是诺华2023年净销售额排名前20的产品。引发了全球对放射性偶联药物的热潮。根据市场调研机构GlobalData发布报告称，2023年放射性药物领域的风险投资交易增长了550%，达到4.08亿美元。而2017年，这一数字仅为6300万美元。纷纷下注的大厂们目前，诺华可谓是放射性偶联药物的龙头企业。诺华在2018年以21亿美元收购Endocyte，一举将Lutathera和Pluvicto收入囊中。此外，诺华还于2017年收购了核医学领域的先驱Advanced Accelerator Applications（AAA）。诺华后续还与多家公司展开了关于放射性药物的高金额合作。2023年10月，礼来斥资14亿美元收购Point Biopharma，获得包括核心资产PNT2002在内的放射性药物管线。PNT2002是一款PSMA靶向配体PSMA-I&T 与Lu-177相结合的偶联药物，用于治疗mCRPC。2023年12月，BMS宣布以36亿美元收购RayzeBio，获得基于α核素的差异化放射性药物技术平台和多款在研创新产品，包括核心资产RYZ101。RYZ101是一款基于α核素的SSTR2靶向偶联物，被开发用于治疗胃肠胰神经内分泌肿瘤和非小细胞肺癌。此外，强生、默沙东、拜耳等大药企业也在放射性药物领域中重金布局。根据Wedbush分析师David Nierengarten报告，随着放射性药物领域的合并和收购势头持续，可能会在短期内看到更多的交易。参考资料：1.https://www.biospace.com/article/astrazeneca-buys-fusion-in-potential-2b-deal-joins-radiopharma-buying-spree/2.https://www.astrazeneca.com/media-centre/press-releases/2024/astrazeneca-to-acquire-fusion.html3.https://fusionpharma.com/targeted-alpha-therapeutics/#本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处·····

放射疗法并购上市批准临床2期临床3期