[11C]ER-176([11C]ER-176) - 药物靶点：TSPO_在研适应症：阿尔茨海默症_专利_临床

概要

基本信息

药物类型

小分子化药、诊断用放射药物

别名

11C-ER176

靶点

TSPO

作用机制

TSPO抑制剂(TSPO蛋白抑制剂)、PET imaging(正电子发射断层成像术增强剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

National Institute on Aging

非在研机构

National Institute of Mental HealthNational Institutes of Health Clinical Center

Mayo Clinic

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C20H20ClN3O

InChIKeyASFLYNMYGAYKON-XFBLKYPGSA-N

CAS号1623028-18-1

关联

13

项与 [11C]ER-176 相关的临床试验

NCT05805839 / Enrolling by invitation临床2期IIT

Advanced MR and PET Imaging in Inflammatory Demyelinating Diseases of the Central Nervous System

This purpose of this study is research the usefulness of MRI with PET/CT imaging for measuring brain inflammation and its relation to Multiple Sclerosis (MS).

开始日期2023-07-10

申办/合作机构

Mayo Clinic

NCT05547880 / RecruitingN/AIIT

CNS Correlates of Extended Sleep Restriction

Chronic sleep restriction is ubiquitous in both the general population and the military. The deleterious effects of sleep loss on human alertness and cognitive performance have been documented in numerous studies dating back to the nineteenth century. Over the past decade, evidence has emerged indicating that chronic sleep restriction may also precipitate deleterious, long lasting neuropathological changes in the brain. The purpose of this study is to determine neuropathological effects of sleep restriction and identify physiological mechanisms that correlate with sleep loss-induced performance impairment.

开始日期2023-05-23

申办/合作机构

Walter Reed Army Institute of Research

[+2]

NCT06384378 / Recruiting临床2期IIT

Central and Peripheral Immune Cross-talk in Alzheimer's Disease and Their Modulation by a Novel Immunotherapy

Inflammation could provide a new focus for therapeutic intervention. In this study, we will measure blood and cerebrospinal fluid (CSF) inflammation biomarkers and compare them to measurements of brain glial activation obtained by positron emission tomography (PET). In addition, we will determine the effect of low-dose interleukin-2 (IL-2) immunotherapy, given over 22 weeks, on these inflammation biomarkers.

开始日期2023-03-17

申办/合作机构

The Methodist Hospital Research Institute

100 项与 [11C]ER-176 相关的临床结果

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100 项与 [11C]ER-176 相关的转化医学

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100 项与 [11C]ER-176 相关的专利（医药）

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7

项与 [11C]ER-176 相关的文献（医药）

2024-06-15·Journal of Labelled Compounds and Radiopharmaceuticals

An Improved HPLC Separation Method for TSPO Radioligand [¹¹C]ER176 Clinical Production

Article

作者: Li, Kang‐Po ; Cai, Hancheng

ABSTRACTMitochondrial membrane translocator protein 18 kDa (TSPO) expression is increased in activated microglia, established as a plausible target of neuroinflammation imaging. [11C]ER176, specifically binding to TSPO, has been developed as the third generation of radioligand for PET imaging of TSPO, which showed the potential in better quantifying neuroinflammation than its predecessors. In the current study, we developed an automated radiosynthesis with an improved HPLC purification method for [11C]ER176 clinical production. The improved HPLC separation was integrated into the automated production of [11C]ER176 using a reverse phase semi‐preparative HPLC column with an isocratic pump and the mixture of methanol and 50 mM ammonium acetate as the mobile phase. The fraction corresponding to [11C]ER176 was collected around 8.5–9.0 min without the risk of getting contaminations from nearby impurities. The automated production process took about 30 min after end of bombardment (EOB) and the quality of the final product [11C]ER176 met all specifications for clinical use based on current US Pharmacopeia and FDA CGMP requirements.

2022-11-01·Drug Development Research

Acetamidobenzoxazolone scaffold as a promising translocator protein (18 kDa, TSPO) marker for neuroinflammation imaging: Advancement in last decennial period

Review

作者: Tiwari, Anjani Kumar ; Zhang, Ming‐Rong ; Adhikari, Anupriya

AbstractInflammation has been linked to the onset and progression of a wide range of neuropathological disorders. The well‐conserved outer mitochondrial membrane 18 kDa translocator protein (TSPO) is perceived as an in vivo neuroinflammation marker. A dearth of a reference region, genetic disparity influencing the ligand's affinity for TSPO, and a substantial signal in the endothelium of the brain veins contributes toward complications in quantifying TSPO positron emission tomography (PET) image. Up to the present time several radiotracers based on different pharmacophore such as (R)[11C]PK11195, [18F]DPA714, [11C]PBR28, [11C]ER176, and many more have been recognized for envisaging the prominent TSPO level observed in neurological conditions. Recently acetamidobenzoxazolone (ABO) scaffold, a bicyclic ring system composed of a phenyl ring fused to a carbamate and its substituted radiolabelled analogues especially at C‐5 position has evidenced encouraging outcomes as next generation of TSPO PET ligands. Diverse ABO framework‐based TSPO ligands have been designed embracing imperative aspects such as lipophilicity, metabolic profile, and capability to penetrate the blood–brain barrier apart from least effect of polymorphism (rs6971). Over the years numerous systematic literature reviews compiling different structural class of TSPO ligands characterized on the grounds of their binding affinity and metabolite profile have been reported but none is especially focused toward a fascinating benzoxazolone scaffold. This review exclusively bestows an overview of the recent advancements on ABO derivatives with neuroinflammation imaging potential and emphases on the structural features accountable for visualizing TSPO in‐vivo with collation of published reports during last 10 years.

2022-07-04·Molecular Pharmaceutics

[¹⁸F]BIBD-239: ¹⁸F-Labeled ER176, a Positron Emission Tomography Tracer Specific for the Translocator Protein

Article

作者: Yan, Jun ; Yu, Ziyue ; Chen, Hualong ; Liu, Yajing ; Wu, Zehui ; Yang, Tingyu ; Jiang, Zeng ; Ji, Xunming ; Zhang, Lu ; Sun, Yuli ; Cheng, Xuebo ; Zheng, Wei

[¹¹C]ER176 has adequate sensitivity to image the human brain translocator protein (TSPO) in all three genotypes by positron emission tomography (PET). However, its clinical application is limited by the short half-life of ¹¹C (20.38 min). To overcome the deficiency of [¹¹C]ER176 and keep the pharmacophore features of ER176 to the maximum extent, we designed four fluorine-labeled ER176 derivatives using the deuterium method. In vitro competition binding confirmed that the designed compounds had high affinity for TSPO. Biodistribution experiments showed that tissues with high expression of TSPO had high uptake of these compounds, as well as that the compound showed high brain penetration and mild defluorination in vivo. Therefore, [¹⁸F]BIBD-239 with simple synthesis conditions was selected for further biological evaluation. Theoretical simulations showed that BIBD-239 and ER176 have similar binding modes and sites to Ala147-TSPO and Thr147-TSPO, which indicated that the tracers may have consistent sensitivity to the three affinity genotypes. In vitro autoradiography and in vivo PET studies of the ischemic rat brain showed dramatically higher uptake of [¹⁸F]BIBD-239 on the lesion site compared to the contralateral side with good brain kinetics. Additionally, [¹⁸F]BIBD-239 provided clear tumor PET images in a GL261 glioma model. Importantly, PET imaging and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) results showed that in vivo defluorination and other metabolites of [¹⁸F]BIBD-239 did not interfere with brain imaging. Conclusively, [¹⁸F]BIBD-239, similar to ER176 with low polymorphism sensitivity, has simple labeling conditions, high labeling yield, high affinity, and high specificity for TSPO, and it is planned for further evaluation in higher species.

100 项与 [11C]ER-176 相关的药物交易

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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
阿尔茨海默症	临床2期	美国	National Institute on Aging	2021-05-11
糖尿病性胃轻瘫	临床2期	美国	Mayo Clinic	2021-05-10
类风湿关节炎	临床2期	美国	National Institute of Mental Health	2019-06-14
类风湿关节炎	临床2期	美国	National Institutes of Health Clinical Center	2019-06-14
痴呆	临床前	美国	National Institute of Mental Health	2019-07-03
痴呆	药物发现	美国	National Institutes of Health Clinical Center	2019-07-03
肌炎	药物发现	美国	National Institute of Mental Health	2019-06-14
肌炎	药物发现	美国	National Institutes of Health Clinical Center	2019-06-14

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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


NCT03958630 (CTgov)	临床1期	神经系统变性病 \| 神经炎症 \| 痴呆	13	Positron Emission Tomography (PET) Scan+11C-ER176+11C-PIB (Healthy Volunteers)	襯顧選衊窪醖選淵憲簾(築壓獵憲襯齋夢壓範蓋) = 遞廠鹹鹹觸淵齋齋獵範窪範簾積範願製衊衊廠 (遞觸積廠衊鏇鏇衊築壓, 願衊蓋膚觸淵鹽窪鏇獵 ~ 顧襯襯簾遞夢憲蓋積積) 更多	-	2024-05-01
				Positron Emission Tomography (PET) Scan+11C-ER176+11C-PIB (Subjects With Frontotemporal Dementia (FTD))	襯顧選衊窪醖選淵憲簾(築壓獵憲襯齋夢壓範蓋) = 淵膚窪網選鏇製構衊襯窪範簾積範願製衊衊廠 (遞觸積廠衊鏇鏇衊築壓, 選蓋醖廠齋艱壓膚繭製 ~ 製獵艱簾艱壓蓋鹽鹽窪) 更多
NCT03744312 (CTgov)	临床1/2期	阿尔茨海默症 \| 炎症	9	Florbetaben+11C-ER176 (Cognitive Impairment)	鹹選網淵鏇淵顧壓築窪(廠醖廠選鬱構艱簾艱鑰) = 淵淵鹽鏇蓋壓簾鹹鹽繭積醖夢鏇構憲憲淵艱襯 (蓋構鬱鬱積觸膚鹹淵選, 壓廠齋遞壓鹹繭窪顧構 ~ 繭遞鹽簾餘鬱獵構襯製) 更多	-	2023-09-13
				Florbetaben+11C-ER176 (No Cognitive Impairment)	鹹選網淵鏇淵顧壓築窪(廠醖廠選鬱構艱簾艱鑰) = 餘範繭築鹹範繭鬱觸憲積醖夢鏇構憲憲淵艱襯 (蓋構鬱鬱積觸膚鹹淵選, 鏇鹹簾鑰鏇齋夢糧範選 ~ 遞遞窪夢積鬱鬱鹽選餘) 更多
NCT04762719 (CTgov)	临床2/3期	糖尿病性胃轻瘫	12	Core biopsy of gastric muscle+PET/CT Scan (Diabetic Gastroparesis Subjects)	糧餘蓋製壓積網鑰廠鹹(範壓觸簾醖鏇壓餘醖網) = 構蓋醖鬱鏇憲積鑰範窪淵築壓鹽願獵壓觸糧鬱 (積壓鑰製糧遞糧製製積, 蓋積簾餘簾夢膚鹽網鹽 ~ 艱顧獵遞壓積淵遞鹽窪) 更多	-	2023-04-18
				PET/CT Scan (Diabetic Without Gastroparesis Subjects)	糧餘蓋製壓積網鑰廠鹹(範壓觸簾醖鏇壓餘醖網) = 獵選製壓鏇構鬱觸壓蓋淵築壓鹽願獵壓觸糧鬱 (積壓鑰製糧遞糧製製積, 繭製積鬱鬱壓製膚窪製 ~ 淵簾鑰壓選簾繭艱獵艱) 更多
SNMMI2022	N/A	-	-	11C-ER176 (High-affinity binders)	鬱鹽簾範蓋鏇糧糧襯淵(鹹範獵夢選襯淵鏇遞糧) = ICC was excellent. Variability and ICC were good even in small VOIs and PVC did not affect the results. 範構鏇遞網膚選鹹蓋選 (艱廠淵蓋糧襯廠鬱窪積 ) 更多	-	2022-08-08
				11C-ER176 (Mixed-affinity binders)