18F-αvβ6-Binding-Peptide(18F-αvβ6-Binding-Peptide) - 在研适应症：脑转移瘤，转移性非小细胞肺癌，肿瘤_专利_临床

概要

基本信息

药物类型

多肽偶联核素、诊断用放射药物

别名

靶点-

作用机制

PET imaging(正电子发射断层成像术增强剂)

治疗领域

肿瘤神经系统疾病呼吸系统疾病+ [4]

在研适应症

脑转移瘤转移性非小细胞肺癌肿瘤+ [5]

非在研适应症-

原研机构

National Cancer Institute

在研机构

National Cancer Institute

University of California, Davis

National Institutes of Health

非在研机构-

最高研发阶段临床1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

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关联

3

项与 18F-αvβ6-Binding-Peptide 相关的临床试验

NCT05452005 / Recruiting临床1期IIT

Fluorine-18-AlphaVBeta6-Binding Peptide Positron Emission Tomography for Staging, Response Assessment, and Patient Selection in Metastatic Non-Small Cell Lung Cancer

This study investigates fluorine-18-AlphaVBeta6-BP ([18F]-αvβ6-BP) as a Positron Emission (PET) imaging agent in Non-Small Cell Lung Cancer (NSCLC) patients with brain metastases. Investigators hypothesize that [18F]-αvβ6-BP PET/Computed Tomography (CT) is a sensitive tool for disease assessment in patients with metastatic NSCLC, including those with brain metastases.

开始日期2022-09-13

申办/合作机构

University of California, Davis

[+1]

NCT04376593 / Enrolling by invitation早期临床1期IIT

18F-αvβ6-binding-peptide PET/CT in Patients Post SARS CoV2 Infection

This is a PET/CT study using the 18F-αvβ6-binding-peptide.The goal of this study is to evaluate this peptide in patients after infection with SARS CoV2.

开始日期2020-05-01

申办/合作机构

University of California, Davis

NCT03164486 / Active, not recruiting早期临床1期IIT

First-in-Human Positron Emission Tomography Study Using the 18F-αvβ6-Binding-Peptide

This clinical trial studies the side effects of 18F-alphavbeta6-binding-peptide and how well it works in imaging patients with primary or cancer that has spread to the breast, colorectal, lung, or pancreatic. Radiotracers, such as 18F-alphavbeta6-binding-peptide, may improve the ability to locate cancer in the body.

开始日期2016-11-01

申办/合作机构

University of California, Davis

[+1]

100 项与 18F-αvβ6-Binding-Peptide 相关的临床结果

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100 项与 18F-αvβ6-Binding-Peptide 相关的转化医学

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100 项与 18F-αvβ6-Binding-Peptide 相关的专利（医药）

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11

项与 18F-αvβ6-Binding-Peptide 相关的文献（医药）

2023-02-17·Toxicological Sciences

Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

Article

作者: Luus, Lia ; Stawski, Lukasz ; Montesinos, Monica S ; Carr, Tracy ; Ray, Adrian S ; Kambara, Takahito ; Trela, Bruce ; Lu, Min ; Maisonave, Kevin ; Guffroy, Magali ; Olson, Lauren ; Hazelwood, Lisa A ; He, Yupeng ; Chen, Huidong

AbstractAdministration of a novel and selective small molecule integrin αvβ6 inhibitor, MORF-627, to young cynomolgus monkeys for 28 days resulted in the rapid induction of epithelial proliferative changes in the urinary bladder of 2 animals, in the absence of test agent genotoxicity. Microscopic findings included suburothelial infiltration by irregular nests and/or trabeculae of epithelial cells, variable cytologic atypia, and high mitotic rate, without invasion into the tunica muscularis. Morphologic features and patterns of tumor growth were consistent with a diagnosis of early-stage invasive urothelial carcinoma. Ki67 immunohistochemistry demonstrated diffusely increased epithelial proliferation in the urinary bladder of several monkeys, including those with tumors, and αvβ6 was expressed in some epithelial tissues, including urinary bladder, in monkeys and humans. Spontaneous urothelial carcinomas are extremely unusual in young healthy monkeys, suggesting a direct link of the finding to the test agent. Inhibition of integrin αvβ6 is intended to locally and selectively block transforming growth factor beta (TGF-β) signaling, which is implicated in epithelial proliferative disorders. Subsequent in vitro studies using a panel of integrin αvβ6 inhibitors in human bladder epithelial cells replicated the increased urothelial proliferation observed in monkeys and was reversed through exogenous application of TGF-β. Moreover, analysis of in vivo models of liver and lung fibrosis revealed evidence of epithelial hyperplasia and cell cycle dysregulation in mice treated with integrin αvβ6 or TGF-β receptor I inhibitors. The cumulative evidence suggests a direct link between integrin αvβ6 inhibition and decreased TGF-β signaling in the local bladder environment, with implications for epithelial proliferation and carcinogenesis.

2023-01-01·Frontiers in oncology

In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis.

Article

作者: Li, Deling ; Ai, Lin ; Jia, Wang ; Li, Baowang ; Fan, Di ; Zhang, Chengkai ; Luo, Qi

IntroductionIntegrin αvβ6, which is upregulated in malignancies and remains absent or weak in normal tissue, is a promising target in molecular imaging therapeutics. In vivo imaging of integrin αvβ6 could therefore be valuable for early tumor detection and intraoperative guidance.MethodsIn this study, integrin αvβ6-targeting probe G2-SFLAP3 was labeled with near-infrared (NIR) dye Cy5.5 or radioisotope 68Ga. The resulting probes were evaluated in integrin αvβ6-positive A549 and αvβ6-negative H1703 xenograft mice models.ResultsThe cellar uptake of G2-SFLAP3-Cy5.5 was consistent with the expression of integrin αvβ6. Both subcutaneous and brain metastatic A549 tumors could be clearly visualized by NIR fluorescent imaging of G2-SFLAP3-Cy5.5. A549 tumors demonstrated the highest G2-SFLAP3-Cy5.5 accumulation at 4h post-injection (p.i.) and remain detectable at 84h p.i. The fluorescent signal of G2-SFLAP3-Cy5.5 was significantly reduced in H1703 and A549-blocking groups. Consistently, small-animal PET imaging showed tumor-specific accumulation of 68Ga-DOTA-G2-SFLAP3.DiscussionG2-SFLAP3 represents a promising agent for noninvasive imaging of non-small cell lung cancer (NSCLC) and brain metastases.

2021-12-01·European Journal of Pharmacology3区 · 医学

Pharmacological characterisation of GSK3335103, an oral αvβ6 integrin small molecule RGD-mimetic inhibitor for the treatment of fibrotic disease

3区 · 医学

Article

作者: Jenkins, R Gisli ; Borthwick, Lee A ; Burgoyne, Rachel A ; John, Alison E ; Barrett, John W ; Barksby, Ben S ; Hatley, Richard J D ; Slack, Robert J ; Man, Yim ; Marshall, Richard P ; Barrett, Tim N ; Luckett, Jeni C ; Macdonald, Simon J F ; Roper, James A ; Wilkinson, Alex L ; Barnes, Rory ; Fisher, Andrew J ; Morrison, Valerie S ; Gower, E ; Pun, K Tao ; Procopiou, Panayiotis A

Fibrosis is the formation of scar tissue due to injury or long-term inflammation and is a leading cause of morbidity and mortality. Activation of the pro-fibrotic cytokine transforming growth factor-β (TGFβ) via the alpha-V beta-6 (αvβ6) integrin has been identified as playing a key role in the development of fibrosis. Therefore, a drug discovery programme to identify an orally bioavailable small molecule αvβ6 arginyl-glycinyl-aspartic acid (RGD)-mimetic was initiated. As part of a medicinal chemistry programme GSK3335103 was identified and profiled in a range of pre-clinical in vitro and in vivo systems. GSK3335103 was shown to bind to the αvβ6 with high affinity and demonstrated fast binding kinetics. In primary human lung epithelial cells, GSK3335103-induced concentration- and time-dependent internalisation of αvβ6 with a rapid return of integrin to the cell surface observed after washout. Following sustained engagement of the αvβ6 integrin in vitro, lysosomal degradation was induced by GSK3335103. GSK3335103 was shown to engage with the αvβ6 integrin and inhibit the activation of TGFβ in both ex vivo IPF tissue and in a murine model of bleomycin-induced lung fibrosis, as measured by αvβ6 engagement, TGFβ signalling and collagen deposition, with a prolonged duration of action observed in vivo. In summary, GSK3335103 is a potent αvβ6 inhibitor that attenuates TGFβ signalling in vitro and in vivo with a well-defined pharmacokinetic/pharmacodynamic relationship. This translates to a significant reduction of collagen deposition in vivo and therefore GSK3335103 represents a potential novel oral therapy for fibrotic disorders.

100 项与 18F-αvβ6-Binding-Peptide 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
脑转移瘤	临床1期	美国	University of California, Davis	2022-09-13
转移性非小细胞肺癌	临床1期	美国	University of California, Davis	2022-09-13
新型冠状病毒感染	临床1期	美国	University of California, Davis	2020-05-01
乳腺癌	临床1期	美国	National Cancer Institute	2016-11-01
结直肠癌	临床1期	美国	National Cancer Institute	2016-11-01
胰腺腺泡癌	临床1期	美国	National Cancer Institute	2016-11-01
继发性肺恶性肿瘤	临床1期	美国	National Cancer Institute	2016-11-01
肿瘤	临床1期	-	National Institutes of Health	-