11C-UCB-J(11C-UCB-J) - 药物靶点：SV2A_在研适应症：大麻滥用，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

UCB-J

+ [1]

靶点

SV2A

作用机制

SV2A调节剂(突触囊泡蛋白2A调节剂)

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 Drug Abuse

非在研机构

Alkermes Plc

UCB Pharma GmbH

最高研发阶段临床1/2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C17H15F3N2O

InChIKeyRFSDYRVOGWHOFT-XOTOJZTHSA-N

CAS号2098041-11-1

关联

7

项与 11C-UCB-J 相关的临床试验

NCT05586581 / Recruiting临床1/2期IIT

PET Imaging of Synaptic Density Combined with Neuroimmunologic Measures to Reveal Mechanisms of HIV Neuropathogenesis During ART

The purpose of this study is to longitudinally characterize and evaluate changes in synaptic density in the brain using novel positron-emission tomography (PET) scans; magnetic resonance imaging (MRI), and clinical laboratory markers associated with HIV-related injury in the central nervous system. This study will test hypotheses relating to the presence and mechanisms of aberrant brain structure at the synaptic level in living humans with virologically controlled HIV on antiretroviral therapy. To evaluate associations between PET imaging radiotracers [11C]UCB-J, a ligand for presynaptic vesicle protein 2A (SV2A), a vesicle membrane protein expressed in synapses, and PET [11C]PBR28 a measure of microglia function in the brain, the Yale PET center has developed an advanced approach of combining multiple distinct ligands in coordinated same-day PET imaging. Additionally, the study will evaluate the associations of this novel synaptic density marker with well-established clinical measures of neurocognitive performance and laboratory measures of blood and cerebrospinal fluid (CSF).

开始日期2023-05-17

申办/合作机构

Yale University

[+2]

NCT05465538 / Recruiting临床1/2期IIT

Effect of Cannabis Use on Synaptic Density in Older Adults

The aim of the study is to examine the effect of cannabis use on brain synaptic density among older adults using [11C]UCB-J PET imaging.

开始日期2022-07-06

申办/合作机构

Yale University

[+1]

NCT05472818 / Recruiting早期临床1期IIT

SV2A Density Cannabis Use Disorder

The main purpose of this study is to determine whether hippocampal synaptic vesicle density estimated by hippocampal [11C]APP-311/[11C]UCB-J binding in individuals diagnosed with cannabis use disorder (CUDs) improves with at least 4 weeks of confirmed abstinence from cannabis, in comparison to healthy controls (HCs). Furthermore, any change in synaptic vesicle density will be placed in functional context by measuring verbal memory, which is sensitive to hippocampal function, before and after at least 4 weeks of confirmed abstinence. Finally, the relationship between hippocampal [11C]UCB-J binding in CUDs with measures of cannabis exposure (e.g., age of initiation, cumulative lifetime dose) will be explored.

开始日期2022-05-01

申办/合作机构

Yale University

[+1]

100 项与 11C-UCB-J 相关的临床结果

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100 项与 11C-UCB-J 相关的转化医学

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100 项与 11C-UCB-J 相关的专利（医药）

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42

项与 11C-UCB-J 相关的文献（医药）

2024-09-01·Neuropharmacology

Excessive sucrose consumption reduces synaptic density and increases cannabinoid receptors in Göttingen minipigs

Article

作者: Bærentzen, Simone Larsen ; Thomsen, Majken Borup ; Alstrup, Aage Ko ; Brooks, David J ; Landau, Anne M ; Wegener, Gregers ; Winterdahl, Michael

Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and metabolic syndrome. Clinical studies link unhealthy diets with the development of mental health disorders, particularly depression. Here, we investigate the effects of 12 days of sucrose consumption administered as 2 L of 25% sucrose solution daily for 12 days in Göttingen minipigs on the function of brain receptors involved in reward and motivation, regulating feeding, and pre- and post-synaptic mechanisms. Through quantitative autoradiography of cryostat sections containing limbic brain regions, we investigated the effects of sucrose restricted to a 1-h period each morning, on the specific binding of [³H]raclopride on dopamine D2/3 receptors, [³H]UCB-J at synaptic vesicle glycoprotein 2A (SV2A), [³H]MPEPγ at metabotropic glutamate receptor subtype 5 (mGluR5) and [³H]SR141716A at the cannabinoid receptor 1 (CB1). Compared to control diet animals, the sucrose group showed significantly lower [³H]UCB-J and [³H]MPEPγ binding in the prefrontal cortex. The sucrose-consuming minipigs showed higher hippocampal CB1 binding, but unaltered dopamine D2/3 binding compared to the control group. We found that the sucrose diet reduced the synaptic density marker while increasing CB1 binding in limbic brain structures, which may subserve maladaptive changes in appetite regulation and feeding. Further studies of the effects of diets and lifestyle habits on brain neuroreceptor and synaptic density markers are warranted.

2024-05-15·ACS Chemical Neuroscience

Exploring the Interactions between two Ligands, UCB-J and UCB-F, and Synaptic Vesicle Glycoprotein 2 Isoforms

Article

作者: Varrone, Andrea ; Zou, Rongfeng ; Ågren, Hans ; Li, Junhao ; Halldin, Christer ; Nag, Sangram

In silico modeling was applied to study the efficiency of two ligands, namely, UCB-J and UCB-F, to bind to isoforms of the synaptic vesicle glycoprotein 2 (SV2) that are involved in the regulation of synaptic function in the nerve terminals, with the ultimate goal to understand the selectivity of the interaction between UCB-J and UCB-F to different isoforms of SV2. Docking and large-scale molecular dynamics simulations were carried out to unravel various binding patterns, types of interactions, and binding free energies, covering hydrogen bonding and nonspecific hydrophobic interactions, water bridge, π-π, and cation-π interactions. The overall preference for bonding types of UCB-J and UCB-F with particular residues in the protein pockets can be disclosed in detail. A unique interaction fingerprint, namely, hydrogen bonding with additional cation-π interaction with the pyridine moiety of UCB-J, could be established as an explanation for its high selectivity over the SV2 isoform A (SV2A). Other molecular details, primarily referring to the presence of π-π interactions and hydrogen bonding, could also be analyzed as sources of selectivity of the UCB-F tracer for the three isoforms. The simulations provide atomic details to support future development of new selective tracers targeting synaptic vesicle glycoproteins and their associated diseases.

2024-04-01·Alzheimer's & Dementia

Tracing synaptic loss in Alzheimer's brain with SV2A PET‐tracer UCB‐J

Article

作者: Kumar, Amit ; Scarpa, Miriam ; Nordberg, Agneta

AbstractINTRODUCTIONSynaptic loss is an early prominent feature of Alzheimer's disease (AD). The recently developed novel synaptic vesicle 2A protein (SV2A) PET‐tracer UCB‐J has shown great promise in tracking synaptic loss in AD. However, there have been discrepancies between the findings and a lack of mechanistic insight.METHODSHere we report the first extensive pre‐clinical validation studies for UCB‐J in control (CN; n = 11) and AD (n = 11) brains using a multidimensional approach of post‐mortem brain imaging techniques, radioligand binding, and biochemical studies.RESULTS AND DISCUSSIONWe demonstrate that UCB‐J could target SV2A protein with high specificity and depict synaptic loss at synaptosome levels in AD brain regions compared to CNs. UCB‐J showed highest synaptic loss in AD hippocampus followed in descending order by frontal cortex, temporal cortex, parietal cortex, and cerebellum. 3H‐UCB‐J large brain‐section autoradiography and cellular/subcellular fractions binding studies indicated potential off‐target interaction with phosphorylated tau (p‐tau) species in AD brains, which could have subsequent clinical implications for imaging studies.Highlights

Synaptic positron emission tomography (PET)–tracer UCB‐J could target synaptic vesicle 2A protein (SV2A) with high specificity in Alzheimer's disease (AD) and control brains.

Synaptic PET‐tracer UCB‐J could depict synaptic loss at synaptosome levels in AD brain regions compared to control.

Potential off‐target interaction of UCB‐J with phosphorylated tau (p‐tau) species at cellular/subcellular levels could have subsequent clinical implications for imaging studies, warranting further investigations.

100 项与 11C-UCB-J 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
大麻滥用	临床2期	美国	National Institute on Drug Abuse	2022-07-06
阿尔茨海默症	临床1期	-	UCB SA	-
亨廷顿舞蹈病	临床前	比利时	Alkermes Plc	2021-01-14

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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


SNMMI2022	N/A	-	-	[11C]UCB-J (Pd2(dba)3 from Alfa Aesar)	顧獵窪鹽淵衊鹹蓋範構(醖窪構簾淵夢齋選鏇獵) = By using the pre-hydrolyzed precursor, the preparation time saved at least 2 h without compromising the product yields 構糧餘糧鏇齋築壓醖範 (憲簾築衊壓齋膚糧糧簾 )	-	2022-08-08
SNMMI2022	N/A	-	-	[11C]UCB-J (In-house synthesized Pd2(dba)3)		-	2022-08-08
SNMMI2021	N/A	-	-	11C-UCB-J PET	築壓蓋積膚衊蓋鹽網範(遞鏇鹽膚襯遞遞窪構觸) = 0.28 簾遞襯廠簾餘窪壓獵衊 (衊構獵鏇簾鑰選蓋製獵 ) 更多	-	2021-05-18
SNMMI2019	N/A	-	4	11 C-UCB-J (11C-UCB-J)	積鹹廠鹽鑰積餘襯糧齋(窪網鑰製顧衊繭齋網廠) = peak of ~ 10 餘鑰願糧蓋築鹽膚積顧 (窪願遞糧艱製鬱壓壓鹹 )	积极	2019-05-21
SNMMI2018	N/A	-	-	11C-UCB-J PET	願網醖鹽鹹艱膚膚廠簾(願膚壓膚艱鬱製繭糧衊) = 衊憲醖齋憲築範衊醖鑰齋繭壓網積鏇糧艱醖顧 (選鏇餘製鏇積網獵壓齋, 0.6)	-	2018-05-23
SNMMI2018	N/A	-	-	Levetiracetam or brivaracetam	願網醖鹽鹹艱膚膚廠簾(願膚壓膚艱鬱製繭糧衊) = 構鏇簾襯顧獵願淵憲遞齋繭壓網積鏇糧艱醖顧 (選鏇餘製鏇積網獵壓齋, 0.17)	-	2018-05-23
SNMMI2018	N/A	-	-	11C-UCB-J PET	觸範憲願鹹網製鹽襯網(膚夢艱選憲製簾齋憲壓) = 鹽餘積壓範糧鏇夢窪壓簾觸齋襯餘遞壓蓋製餘 (廠觸遞製餘艱衊襯憲願 )	-	2018-05-23
SNMMI2017	N/A	-	-	11 C-UCB-J (2 OSEM iterations)	淵簾築網艱鹹築繭蓋艱(獵鏇構鑰鬱顧遞糧繭齋) = 鏇構鑰簾積廠膚築壓餘衊網製廠窪憲鏇糧窪鏇 (簾積獵築構糧鑰鏇鹹觸 )	-	2017-05-24
SNMMI2017	N/A	-	-	11 C-UCB-J (3 OSEM iterations)	淵簾築網艱鹹築繭蓋艱(獵鏇構鑰鬱顧遞糧繭齋) = 範膚壓餘範鏇範鹽積網衊網製廠窪憲鏇糧窪鏇 (簾積獵築構糧鑰鏇鹹觸 )	-	2017-05-24
SNMMI2015	N/A	-	-	Radiotracer (N-(4-(18F)Fluoro-Benzyl)-6-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)-pyridazine-3-carboxamide ([18F]-FAPPT))	蓋築鹹壓夢齋壓鬱範廠(艱獵壓膚簾獵願築廠遞) = It remained 99% intact out to 3 h 築憲窪廠糧鑰願蓋淵糧 (窪簾簾簾醖蓋夢齋醖鏇 )	-	2015-05-15