BAY-94-9392(BAY-94-9392) - 药物靶点：SLC7A11_在研适应症：同种异体移植排斥反应，胆管癌，肝细胞癌_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

FSPG

+ [1]

靶点

SLC7A11

作用方式

抑制剂、增强剂

作用机制

SLC7A11抑制剂(胱氨酸/谷氨酸转运体抑制剂)、PET imaging(正电子发射断层成像术增强剂)

治疗领域

免疫系统疾病其他疾病肿瘤+ [2]

在研适应症

同种异体移植排斥反应胆管癌肝细胞癌+ [6]

非在研适应症

晚期三阴性乳腺癌B细胞淋巴瘤脑转移瘤+ [23]

原研机构

Piramal Pharma Limited

在研机构

National Cancer Institute

The University of Texas MD Anderson Cancer Center

Bayer HealthCare AG

+ [3]

非在研机构

Bayer HealthCare Pharmaceuticals, Inc.GE Healthcare Holdings, Inc.Life Molecular Imaging Ltd.

+ [2]

权益机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C8H14FNO4

InChIKeyMKDNDKMECWBLOF-XUCPOOORSA-N

CAS号1196963-74-2

关联

14

项与 BAY-94-9392 相关的临床试验

NCT05322135

/ Terminated早期临床1期IIT

A Pilot Study of Glutamine PET Imaging of Head and Neck Squamous Cell Carcinoma

We propose a focused, prospective pilot clinical imaging trial to evaluate 11C-Gln PET/CT followed by 18F-FSPG PET/CT in 20 HNSCC patients. Imaging metrics that are common to PET (e.g. SUVmax, peak or mean) will be determined.
This study will also allow the acquisition of additional safety and biodistribution data, as, to date, only a limited number of patients have been evaluated with 11C-Gln as a direct PET imaging biomarker of Gln uptake. To date, no adverse side effects have been observed. We do not anticipate any toxicity since this tracer is a naturally-occurring essential amino acid in high abundance and is administered at sub-pharmacologic doses.
A long-term goal of these preliminary studies is to validate the utility of Gln PET imaging metrics for HNSCC and to expand this imaging technique to additional patients in prospective cohorts of patients with HNSCC.

开始日期2022-09-14

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT02379377

/ Recruiting临床1期IIT

PET Imaging of Hepatocellular Carcinoma With 18F-FSPG

This clinical trial studies fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) positron emission tomography (PET) in imaging patients with liver cancer before undergoing surgery or transplant. Diagnostic procedures, such as 18F-FSPG PET, may help find and diagnose liver cancer and find out how far the disease has spread.

开始日期2022-02-15

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT03275974

/ Active, not recruiting临床1期IIT

Glutamine PET Imaging of Colorectal Cancer

The clinical trial studies how well 11C-glutamine and 18F-FSPG positron emission tomography (PET) imaging works in detecting tumors in patients with metastatic colorectal cancer compared to standard imaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scanning.

开始日期2021-04-27

申办/合作机构

The University of Texas MD Anderson Cancer Center

100 项与 BAY-94-9392 相关的临床结果

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100 项与 BAY-94-9392 相关的转化医学

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100 项与 BAY-94-9392 相关的专利（医药）

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18

项与 BAY-94-9392 相关的文献（医药）

2023-06-01·Molecular Imaging and Biology

Radiosynthesis and Analysis of (S)-4-(3-[18F]Fluoropropyl)-L-Glutamic Acid

Article

作者: Brown, Gavin ; Soloviev, Dmitry ; Lewis, David Y

Abstract Purpose(S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is an L-glutamate derivative used as a PET biomarker to assess intracellular redox status in vivo through targeting of the cystine/glutamate antiporter protein, xc− transporter. In this report, we describe a radiosynthesis of [18F]FSPG for use in PET studies that address specific challenges in relation to the radiotracer purity, molar activity, and quality control testing methods.ProceduresThe radiosynthesis of [18F]FSPG was performed using a customised RNPlus Research automated radiosynthesis system (Synthra GmbH, Hamburg, Germany). [18F]FSPG was labelled in the 3-fluoropropylmoiety at the 4-position of the glutamic acid backbone with fluorine-18 via substitution of nucleophilic [18F]fluoride with a protected naphthylsulfonyloxy-propyl-L-glutamate derivative. Radiochemical purity of the final product was determined by radio HPLC using a new method of direct analysis using a Hypercarb C18 column.ResultsThe average radioactivity yield of [18F]FSPG was 4.2 GBq (range, 3.4–4.8 GBq) at the end of synthesis, starting from 16 GBq of [18F]fluoride at the end of bombardment (n = 10) in a synthesis time of 50 min. The average molar activity and radioactivity volumetric concentration at the end of synthesis were 66 GBq µmol−1 (range, 48–73 GBq µmol−1) and 343–400 MBq mL−1, respectively.ConclusionStability tests using a 4.6 GBq dose with a radioactivity volumetric concentration of 369 MBq mL−1 at the end of synthesis showed no observable radiolysis 3 h after production. The formulated product is of high radiochemical purity (> 95%) and higher molar activity compared to previous methods and is safe to inject into mice up to 3 h after production.

2022-10-01·Journal of Nuclear Medicine1区 · 医学

PET Imaging of System x_C⁻ in Immune Cells for Assessment of Disease Activity in Mice and Patients with Inflammatory Bowel Disease

1区 · 医学

Article

作者: Jung, Jin Hwa ; Seo, Minjung ; Park, Sang Hyoung ; Kim, Misung ; Hwang, Sung Wook ; Chae, Sun Young ; Na, Sae Jung ; Lee, Dong Yun ; Kim, Jihun ; Lee, Sang Ju ; Kim, Ji Young ; Kim, Seog-Young ; Oh, Seung Jun ; Ye, Byong Duk ; Moon, Dae Hyuk ; Koglin, Norman ; Kweon, Mi-Na ; Stephens, Andrew W ; Kim, Yeji ; Kim, Sang-Yeob

We aimed to explore whether the imaging of antiporter system x_C ^- of immune cells with (4S)-4-(3-¹⁸F-fluoropropyl)-l-glutamate (¹⁸F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: ¹⁸F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer-induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system x_C ^- and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal ¹⁸F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. ¹⁸F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. ¹⁸F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal ¹⁸F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68⁺xCT⁺ and CD3⁺xCT⁺ cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68⁺xCT⁺ cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system x_C ^- in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. ¹⁸F-FSPG PET imaging of system x_C ^- activity may noninvasively assess the IBD activity.

2022-01-01·Theranostics1区 · 医学

Radiotracer stereochemistry affects substrate affinity and kinetics for improved imaging of system x_C^- in tumors

1区 · 医学

ArticleOA

作者: Berndt, Mathias ; Witney, Timothy H ; Kim, Jana ; Khalil, Eman ; Mueller, Andre ; Edwards, Richard ; Koglin, Norman ; Greenwood, Hannah E ; Baark, Friedrich ; Firth, George

Amino acid utilization is perturbed in cancer cells, which rewire their metabolism to support cell survival and proliferation. This metabolic reprogramming can be exploited for diagnostic purposes through positron emission tomography imaging of fluorine-18 labeled amino acids. Despite its promise, little is known regarding transporter-recognition of non-natural amino acid stereoisomers or their utility for cancer imaging. We report here the synthesis and in vivo characterization of a radiolabeled amino acid (R)-4-(3-¹⁸F-fluoropropyl)-ʟ-glutamate ([¹⁸F]FRPG) and compared its tumor imaging properties to the 4S-isomer, [¹⁸F]FSPG. Methods: [¹⁸F]FRPG and [¹⁸F]FSPG uptake was assessed in H460 lung cancer cells, with efflux measured 30 min after removal of exogenous activity. Specificity of [¹⁸F]FRPG for system x_C^- was further examined following transporter inhibition and blocking studies with system x_C^- substrates. [¹⁸F]FRPG and [¹⁸F]FSPG pharmacokinetics was next quantified in mice bearing subcutaneous A549, H460, VCAP and PC3 tumors, with mice bearing A549 tumors imaged by PET/CT. To better-understand differential tumor retention, radiometabolite analysis was performed on tissue and blood samples after imaging. Next, [¹⁸F]FRPG and [¹⁸F]FSPG retention in lipopolysaccharide-treated lungs were compared to an orthotopic H460 lung cancer model. Finally, the sensitivity of [¹⁸F]FRPG to manipulation of the redox environment was examined in cell and in vivo models. Results: [¹⁸F]FRPG was specifically transported across the plasma membrane by the cystine/glutamate antiporter system x_C^- and retained at high levels in multiple tumor models. Conversely, [¹⁸F]FRPG was rapidly extracted from the blood and cleared from tissues with low system x_C^- expression. Due to its favorable imaging properties, tumor-to-blood ratios ≥10 were achieved with [¹⁸F]FRPG, which were either equal to or greater than [¹⁸F]FSPG. In addition, [¹⁸F]FRPG retention in orthotopic lung tumors with high system x_C^- expression was 2.5-fold higher than inflamed tissue, allowing for clear tumor visualization. In vivo, [¹⁸F]FRPG and [¹⁸F]FSPG were metabolized to a single species, with [¹⁸F]FRPG showing a higher percentage of parent radiotracer in tumors compared to [¹⁸F]FSPG. [¹⁸F]FRPG was sensitive to redox manipulations and tumor retention was reduced following treatment with liposomal doxorubicin in mice bearing ovarian tumors. Conclusions: Given the fast clearance and low background retention of [¹⁸F]FRPG throughout the body, this radiotracer holds promise for the imaging of system x_C^- activity and treatment response monitoring in tumors of the thorax, abdomen, and head and neck. [¹⁸F]FRPG PET imaging provides a sensitive noninvasive measure of system x_C^- and excellent properties for cancer imaging.

100 项与 BAY-94-9392 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15041

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
晚期三阴性乳腺癌	临床2期	美国	National Cancer Institute	2015-07-01
B细胞淋巴瘤	临床2期	美国	National Cancer Institute	2015-07-01
3型乳腺癌	临床2期	美国	National Cancer Institute	2015-07-01
间皮瘤	临床2期	美国	National Cancer Institute	2015-07-01
转移性非小细胞肺癌	临床2期	美国	National Cancer Institute	2015-07-01
转移性肾细胞癌	临床2期	美国	National Cancer Institute	2015-07-01
非小细胞肺癌IIIA期	临床2期	美国	National Cancer Institute	2015-07-01
多发性肺结节	临床2期	美国	National Cancer Institute	2015-06-16
尼古丁成瘾	临床2期	美国	National Cancer Institute	2015-06-16
孤立性肺结节	临床2期	美国	National Cancer Institute	2015-06-16

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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


NCT03824535 (CTgov)	临床2期	肺癌 \| 肺结节 \| 多发性肺结节	15	Positron Emission Tomography (PET/CT)+Fludeoxyglucose F-18+Fluorine F 18 L-glutamate Derivative BAY94-9392	窪廠鹹範選壓齋窪餘齋(鹽願鏇艱築網簾觸夢鹹) = 壓夢齋製餘鏇網選簾夢製壓膚積鏇憲憲構窪壓 (網糧範觸鹹蓋構獵網蓋, 餘壓糧製窪壓餘醖築範 ~ 膚鑰範鏇艱選窪積獵遞) 更多	-	2025-04-09
NCT02448225 (CTgov)	临床2期	肺癌 \| 尼古丁成瘾 \| 孤立性肺结节 \| 多发性肺结节	46	fluorodeoxyglucose F-18+Fluorine F 18 L-glutamate Derivative BAY94-9392	繭齋積鹽餘製鑰窪觸鏇(廠壓範構顧淵廠齋壓遞) = 獵衊艱構鏇齋簾醖鹽淵製蓋憲餘範鏇襯網衊製 (壓願廠築艱鬱繭觸鏇窪, 鏇製願鬱製衊醖糧壓構 ~ 鏇選糧夢衊獵鬱餘襯醖) 更多	-	2022-05-10
NCT01103310 \| NCT01186601 (Pubmed \| Clin Cancer Res)	临床1期	复发性前列腺癌 xCT \| CD44	20	18F-FSPG3-[18F]Fluoropropyl)-L-glutamate (18F-FSPG) (18F-FSPG PET)	壓鑰廠鏇醖構蓋艱憲蓋(餘餘憲鹽鹹願鬱鬱遞簾) = 簾顧齋鑰膚艱壓窪遞鏇廠遞襯糧製餘獵艱獵醖 (襯鹽鏇顧衊製鏇窪選蓋 )	积极	2020-10-15
NCT02599194 (CTgov)	临床2期	转移性肾细胞癌 \| 非小细胞肺癌IIIA期 \| 间皮瘤 \| B细胞淋巴瘤 \| 非小细胞肺癌IIIB期 \| 转移性乳腺癌 \| 转移性非小细胞肺癌 \| 晚期三阴性乳腺癌 \| 3型乳腺癌	7	18F-FDG+18F-FSPG	獵鑰艱範醖觸憲夢鑰鬱(膚範膚壓鬱壓願遞夢醖) = 壓積鏇憲夢鹽淵齋壓製膚鹽鬱構繭觸廠鹽鹹艱 (範廠窪襯簾觸繭艱選淵, 網衊顧積窪顧廠選艱範 ~ 齋膚醖觸艱簾範鑰願構) 更多	-	2019-01-03
AACR2012	N/A	肿瘤	-	FSPG (BAY 94-9392)	積膚範憲鏇淵壓遞醖糧(簾築窪膚艱選衊襯繭餘) = significant correlation between FSPG uptake and protein expression of both the xCT subunit and CD44 窪膚齋餘繭鹹網淵夢築 (選壓繭糧襯選觸淵廠鏇 )	-	2012-04-15