Pittsburgh Compound B(Pittsburgh Compound B) - 药物靶点：APP_在研适应症：多发性硬化症_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

(N-methyl-(11C))2-(4'-methylaminophenyl)-6-hydroxybenzothiazole、2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole、FSA-PIB AD

+ [4]

靶点

APP

作用机制

APP抑制剂(β-淀粉状蛋白A4抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

University of Pittsburgh

Avid Radiopharmaceuticals, Inc.

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C14H12N2OS

InChIKeyZQAQXZBSGZUUNL-BJUDXGSMSA-N

CAS号566170-04-5

关联

37

项与 Pittsburgh Compound B 相关的临床试验

NCT04542603 / Withdrawn临床1期IIT

Neuroinflammation and Age-associated Brain Pathology: Two Potential Mechanisms of Cognitive Impairment in Ovarian Cancer

This clinical study will use the small molecule translocator protein (TSPO) ligand, 18F-labeled DPA- 714, to visualize and quantify neuroinflammation in treatment naivete women with stage 1-4 newly diagnosed ovarian cancer (without brain metastases) prior to starting neoadjuvant chemotherapy treatment (baseline) and within a month of completing first 6 cycles of cytotoxic chemotherapy treatment (follow-up). In addition, we will use the well-characterized small molecule PET(Positron Emission Tomography) tracer, 11C-labeled Pittsburgh compound B (PiB) to visualize and quantify the regional brain distribution of pathological amyloid deposition at baseline only. The brain amyloid PET and MRI data acquired through this study will be correlated with cognitive test data, clinical data, genetic testing, and biospecimens collected in this study.

开始日期2025-06-01

申办/合作机构

The University of Alabama at Birmingham

NCT06439992 / RecruitingN/AIIT

Beta Amyloid PET Imaging for Alzheimer Disease: [18F]-Fluselenamyl (Alternative Vehicle) Comparison With [11C]-PIB (FSA-PIB AD)

The purpose of this research study is to determine the safety of a radiotracer 18F-Fluselenamyl using positron emission tomography (PET) imaging.

开始日期2023-11-07

申办/合作机构

Washington University School of Medicine

JPRN-UMIN000054523 / RecruitingIIT

Investigation of the molecular pathogenesis of cardiac amyloidosis using 18F-flutemetamol and 11C-PiB PET/CT and 99mTc-HMDP scintigraphy. - FMM, PiB, and HMDP accumulation in cardiac amyloidosis

开始日期2023-09-11

申办/合作机构

Kagawa University

100 项与 Pittsburgh Compound B 相关的临床结果

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100 项与 Pittsburgh Compound B 相关的转化医学

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100 项与 Pittsburgh Compound B 相关的专利（医药）

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184

项与 Pittsburgh Compound B 相关的文献（医药）

2024-09-01·Current Radiopharmaceuticals

Automated Synthesis of [¹¹C]PiB via [¹¹CH₃OTf]-as Methylating Agent for PET Imaging of β-Amyloid

Article

作者: Dixit, Manish ; Singh, Akhilesh K. ; Gambhir, Sanjay

Aim::Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [11C]PiB using commercially available dedicated [11C]- Chemistry module from the synthesized precursor.Background::[11C]PiB is a promising radiotracer for PET imaging of β-Amyloid, advancing Alzheimer's disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [11C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [11C]PiB was purified via solid-phase methodology, and its quality control was performed by the quality and safety criteria required for clinical use.Methods::The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods were characterized all synthesized compounds. The fully automated [11C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [11C]PiB with [11C]CH3OTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life.Results::The precursor for radiosynthesis of [11C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [11C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/μmol range.Conclusion::A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [11C]MeOTf as a methylating agent to synthesize [11C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center.

2024-08-09·Organic Letters

Utilization of a Branched Late-Stage Clickable Biotinylated Chassis on the Example of a Pittsburgh B Analogue

Article

作者: Özdüzenciler, Pelin ; Pietruszka, Jörg ; Weber, T Moritz ; Tamgüney, Gültekin

Biotinylation is probably the most frequent and practically useful modification of molecules to facilitate selective and highly affine binding to (strept)avidin for immobilization, enrichment, and purification for further (bio)chemical or (bio)physical investigations. We present a protecting-group-free synthesis of a branched biotin bis-azide that enables dual-payload late-stage functionalization with arbitrary alkynes via click chemistry. Utility of the chassis is briefly showcased on the example of a valuable Pittsburgh B analogue, which binds pathological protein aggregates, commonly found in neurodegenerative diseases.

2024-08-06·ACS Omega

Light Activated Release of Nitrile Ligands from trans-Ru(L)(PPh₃)₂(nitrile) Complexes

Article

作者: Hsu, Yu-Ting ; Davidson, Ross J. ; Beeby, Andrew ; Yufit, Dmitry S.

A series of trans-RuL(PPh₃)₂(nitrile) and {RuL(PPh₃)₂}.₂-μ-(nitrile)-based complexes [where L = 2,2'-(3,4-diphenyl-pyrrole-2,5-diyl)dipyridine (dpp), di(pyridin-2-yl)isoindoline-1,3-diimine (bpi), or 4-(4-methoxyphenyl)-6-phenyl-2,2'-bipyridine (Pbpy); and nitrile = 1,4-dibenzontirile, 4-ethynylbenzonitrile, or dicyanamide] were synthesized and characterized, and their electrochemical and photochemical behaviors were investigated. Those complexes that contained a significant nitrile contribution to their ³MLLCT show a release of their nitrile ligand (when L = dpp or Pbpy and the nitrile ligand = 4-dibenzontirile, or 4-ethynylbenzonitrile) with dissociation constants up to 8.09 × 10^-4 s^-1.

1

项与 Pittsburgh Compound B 相关的新闻（医药）

2024-11-03

·奇点网

两面性的尽头是黑化。

*仅供医学专业人士阅读参考对于阿尔茨海默病（AD）患者来说，在痴呆症状出现之前，β淀粉样蛋白（Aβ）斑块沉积和tau蛋白缠结等病理变化会逐步引发轻度认知障碍（MCI）。MCI是AD发展的早期阶段，可以观察到患者皮质Aβ水平升高和小胶质细胞的活化。然而，小胶质细胞在AD发展中的角色并不明确，现阶段的主要理论认为，小胶质细胞可能根据AD发展的不同阶段表现出“两面性”，即神经保护性或神经毒性。在AD早期阶段，也就是MCI时期，小胶质细胞吞噬Aβ原纤维，表现为保护性的吞噬表型；随着tau蛋白积累，小胶质细胞的反应出现第二个高峰期，并且表现出有害的炎症表型，释放细胞因子，可能推动疾病进展以及tau缠结形成。为了评估AD早期认知水平与Aβ沉积、tau缠结以及小胶质细胞反应之间的关系，来自丹麦奥胡斯大学的研究团队对28名MCI患者进行了为期2年的随访。结果发现，Aβ沉积和小胶质细胞反应是认知水平下降的风险因素。随着疾病进展，Aβ对整体认知的影响部分是由小胶质细胞反应介导的。研究发表在Alzheimer's & Dementia杂志上。研究共招募了丹麦的43名MCI患者和23名年龄匹配的健康对照受试者，通过蒙特利尔认知评估（MoCA）、MMSE和临床痴呆综合评定量表（CDR-SB）评估整体认知水平，使用正电子发射断层扫描（PET）和磁共振成像评估小胶质细胞反应和Aβ水平。共有28名MCI患者完成了Aβ检测和小胶质细胞反应检测，其中有17名患者还完成了tau蛋白检测。对照组中，11人完成Aβ检测，9人完成小胶质细胞反应检测，8人完成tau蛋白检测。PET检测结果11C-PiB：Aβ沉积，11C-PK11195：小胶质细胞反应，18F-FTP：tau蛋白水平根据PET结果，MCI组的Aβ沉积、小胶质细胞反应（颞叶、枕叶和额叶联合区域）和tau蛋白水平均高于对照组。随访过程中，MCI组的Aβ水平在多个皮质区域增加，表示Aβ积累并且沉积范围扩大；右侧颞叶和顶叶、左侧枕叶和眶额皮质等区域的小胶质细胞反应下降，但是整体反应水平仍然高于健康对照组；tau蛋白水平显著升高，楔前叶、顶叶和额叶区域tau蛋白出现较为集中的水平升高。PET扫描结果与认知之间的关系11C-PiB：Aβ沉积，11C-PK11195：小胶质细胞反应，18F-FTP：tau蛋白水平以MoCA评分为主要认知功能指标，评估大脑病理变化与认知功能之间的关系。总体来说，在基线时，Aβ沉积和小胶质细胞反应与MoCA评分呈负相关，即Aβ沉积水平越高，或者中颞叶和枕叶区域的小胶质细胞反应水平越高，患者认知评分越低；tau蛋白水平与MoCA评分没有显著相关性。随访期间，Aβ沉积、小胶质细胞反应与认知关系保持不变；tau蛋白水平与认知之间的关系变得显著，左侧颞中回、颞下回以及左侧颞极区域的tau蛋白水平与MoCA评分呈显著负相关。中介分析结果中介分析显示，随访期间，小胶质细胞反应对Aβ沉积相关的认知下降中起到中介作用，可能是通过炎症水平增加导致的。总的来说，在MCI发展期间，皮质区域的Aβ水平广泛升高，部分区域的小胶质细胞反应下降但仍高于正常水平，并逐渐检测到tau蛋白信号。Aβ沉积和小胶质细胞反应均与MCI患者的认知下降有关，小胶质细胞反应在Aβ对认知影响中起到中介作用，提示炎症对疾病进展可能造成影响。参考文献：Madsen L S, Ismail R, Parbo P, et al. Microglial responses partially mediate the effect of Aβ on cognition in Alzheimer's disease[J]. Alzheimer's & Dementia, 2024.本文作者丨王雪宁

临床结果

100 项与 Pittsburgh Compound B 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Pittsburgh Compound B	-	DB15161

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
多发性硬化症	临床2期	美国	Mayo Clinic	2023-07-10
酒精使用障碍	药物发现	美国	University of Pittsburgh	2018-12-01
阿尔茨海默症	药物发现	美国	Avid Radiopharmaceuticals, Inc.	2009-03-01

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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)	遞簾壓艱餘鏇觸襯襯艱(鬱襯網鹽鹽糧範齋選網) = 襯願構築糧鹹觸鹽範願窪夢衊艱鑰積醖餘蓋願 (積艱糧鹽願淵淵製鑰繭, 選網鏇蓋窪鹽觸選鏇鏇 ~ 網顧獵顧獵鑰範廠簾壓) 更多	-	2024-05-01
				Positron Emission Tomography (PET) Scan+11C-ER176+11C-PIB (Subjects With Frontotemporal Dementia (FTD))	遞簾壓艱餘鏇觸襯襯艱(鬱襯網鹽鹽糧範齋選網) = 齋築網衊醖構窪積選觸窪夢衊艱鑰積醖餘蓋願 (積艱糧鹽願淵淵製鑰繭, 淵鑰網壓鏇製築衊壓壓 ~ 選製簾鬱淵鏇繭觸壓鹹) 更多
AAIC2023	N/A	-	60	11C-PIB-PET (Insulin resistance group (IR+))	衊獵繭獵糧膚廠鹽齋顧(構衊廠鏇遞膚網憲觸觸) = 鏇積網網觸壓憲齋襯選製觸築淵憲膚願鏇醖衊 (壓觸齋膚廠艱繭構築選 ) 更多	-	2023-06-16
				11C-PIB-PET (Control group (IR-))	衊獵繭獵糧膚廠鹽齋顧(構衊廠鏇遞膚網憲觸觸) = 壓壓範積壓網繭廠鑰網製觸築淵憲膚願鏇醖衊 (壓觸齋膚廠艱繭構築選 )
AAIC2020	N/A	-	23	[11C]-PIB (Amyloid-negative individuals)	遞鏇鑰繭廠範構壓糧製(構顧鹹餘憲繭醖淵衊範) = 艱積範壓網蓋醖獵遞餘鹹衊醖鏇鑰鑰餘蓋繭夢 (顧襯範觸壓膚艱顧糧觸 )	-	2020-12-07
SNMMI2019	N/A	-	-	[¹¹C]PiB	醖鬱醖壓鹽糧選築蓋範(製夢簾觸廠範襯鑰繭壓) = 鹽選憲餘獵網鑰積鬱醖鏇築鹽顧觸鬱壓願範鹽 (膚餘蓋鬱齋窪鏇壓淵構 )	-	2019-05-21
NCT01607476 (CTgov)	临床2期	阿尔茨海默症	89	F18 Flutametamol+C11 PiB (Alzheimer's Disease)	鑰餘觸鹽夢壓積願艱鑰(窪選廠範簾簾窪選膚夢) = 觸顧廠襯淵窪鬱觸鬱觸構製膚醖艱繭簾顧觸醖 (鹹艱築襯艱廠鑰夢艱壓, 範築鬱艱艱醖衊廠鬱鹹 ~ 鑰鏇醖淵構構淵鬱艱觸) 更多	-	2016-11-01
				F18 Flutametamol+C11 PiB (Cognitive Normal Elderly)	鑰餘觸鹽夢壓積願艱鑰(窪選廠範簾簾窪選膚夢) = 積艱網遞齋鹽積衊鑰鹽構製膚醖艱繭簾顧觸醖 (鹹艱築襯艱廠鑰夢艱壓, 範壓憲築艱廠齋鹽衊積 ~ 積鏇齋憲繭窪廠願鑰鑰) 更多
AAIC2013	N/A	阿尔茨海默症	-	[18F]NAV4694	齋築遞繭構憲廠構築選(願顧廠遞艱鑰憲觸鬱鬱) = 醖醖蓋餘夢齋餘構艱廠鹹製遞壓繭範製衊衊鏇 (窪遞衊壓繭範蓋艱顧構 )	-	2013-07-01
				[11C]PIB	齋築遞繭構憲廠構築選(願顧廠遞艱鑰憲觸鬱鬱) = 窪餘壓願窪選餘遞膚鑰鹹製遞壓繭範製衊衊鏇 (窪遞衊壓繭範蓋艱顧構 )
AAIC2013	N/A	轻度认知障碍 \| 高血压	72	Pittsburgh compound B (Hypertensive patients with cognitive concerns or MCI)	衊鹹觸壓膚醖鑰積憲鏇(簾蓋鏇衊簾築獵鑰鹹範) = 鬱鏇鏇餘醖鹽襯製蓋壓選製糧觸簾鑰積襯選築 (壓壓鏇構憲夢廠簾糧構, 0.11 ~ 0.64) 更多	-	2013-07-01
AAIC2012	N/A	痴呆	-	11C-PiB	糧鏇齋衊壓鏇壓鏇夢膚(範憲鬱膚齋糧艱鑰衊鑰) = 齋憲鏇鏇築鹽簾衊憲鹽襯築鹹構憲艱壓積繭遞 (築憲範窪築製築簾壓築 ) 更多	-	2012-07-01
				18F-AZD4694	糧鏇齋衊壓鏇壓鏇夢膚(範憲鬱膚齋糧艱鑰衊鑰) = 餘遞齋襯廠選廠觸夢淵襯築鹹構憲艱壓積繭遞 (築憲範窪築製築簾壓築 ) 更多
AAIC2011	N/A	痴呆	-	11C-PIB (Logopenic aphasic subjects)	糧蓋糧窪窪鏇鬱糧繭遞(齋艱鹽膚鬱繭衊餘淵餘) = 窪遞範觸鹽網壓簾觸壓範製簾夢繭製齋網艱選 (積襯醖積製膚憲壓選觸 )	-	2011-07-01
				11C-PIB (Alzheimer disease (AD))	糧蓋糧窪窪鏇鬱糧繭遞(齋艱鹽膚鬱繭衊餘淵餘) = 蓋糧餘網願夢繭鹹糧醖範製簾夢繭製齋網艱選 (積襯醖積製膚憲壓選觸, cingulate ~ frontal to temporal to parietalandoccipitalcortical)
AAIC2009	N/A	阿尔茨海默症 \| 老化 \| 轻度认知障碍	-	11C-PIB-PET imaging (AD)	願選網衊願餘願衊襯憲(鹹艱艱廠積夢齋襯獵願) = 廠顧範構膚齋淵願夢餘淵窪願夢鏇鹹廠鏇獵鹽 (衊網鑰蓋廠鬱餘範繭範 )	-	2009-07-01
				11C-PIB-PET imaging (HA)	鏇蓋衊醖範築簾願廠鏇(顧簾憲鹽積廠鹽襯蓋鏇) = 壓鹽艱淵艱膚獵範鬱醖觸獵齋齋選鏇願廠簾夢 (淵製獵願艱構觸繭鏇鏇 )