cRGD-ZW800-1(cRGD-ZW800-1) - 药物靶点：Integrin x αvβ1 x αvβ3 x αvβ5 x αvβ6 x αvβ8_在研适应症：头颈部鳞状细胞癌，口腔鳞状细胞癌_专利_临床

概要

基本信息

药物类型

多肽偶联药物（PDC）、荧光偶联药物

别名-

靶点

Integrin x αvβ1 x αvβ3 x αvβ5 x αvβ6 x αvβ8

作用机制

整合素家族调节剂、αvβ1抑制剂(整合素α-V/β-1复合体抑制剂)、αvβ3拮抗剂(整合素α-V/β-3复合体拮抗剂)

+ [4]

治疗领域

肿瘤口颌疾病其他疾病

在研适应症

头颈部鳞状细胞癌口腔鳞状细胞癌

非在研适应症-

原研机构

Curadel

在研机构

Erasmus MCCuradel

非在研机构-

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-

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结构

分子式C78H106N13O16S2

InChIKeyYKVVVECWJGQERY-ZVIXCXBOSA-O

CAS号1239855-63-0

使用我们的XDC技术数据为新药研发加速。

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序列信息

Sequence Code 1507071

关联

5

项与 cRGD-ZW800-1 相关的临床试验

NL-OMON54735 / Recruiting临床2期IIT

FLUOPANC-trial - Intraoperative near-infrared fluorescence imaging in pancreatic- and extrahepatic bile duct tumors using cRGD-ZW800-1 and dedicated imaging systems: A phase II feasibility, dose-ranging and optimal dose-(interval) selection trial - FLUOPANC-trial

开始日期2022-11-24

申办/合作机构-

NCT05518071 / Completed临床2期IIT

Intraoperative Near-infrared Fluorescence Imaging in Pancreatic- and Extrahepatic Bile Duct Tumors Using cRGD-ZW800-1 and Dedicated Imaging Systems: A Phase II Feasibility Testing, Dose-ranging and Optimal Dose-(Interval) Selection Trial

Pancreas as well as Cholangiocarcinoma have a dismal prognosis at time of diagnosis, due to late onset of clinical symptoms, patients present with advance disease. Complete surgical resection is the only potential curative treatment, however only a small percentage is eligible for upfront total surgical resection due to extension into anatomical related important vascular structures. Neoadjuvant chemo(radio)therapy has become the standard treatment modality for non-primary resectable disease (borderline resectable and locally advanced pancreatic cancer (LAPC)), where subsequent downstaging can make identification of the primary tumor more challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by providing real-time visualization of tumors, suspect lymph nodes and vital structures during surgery. Additional intra-operative feedback could possibly reduce the frequency of positive resection margins and increase complete removal of locally spread tumor and involved lymph nodes and could thereby improve patient outcomes as well as overall survival. cRGD-ZW800-1 is a targeted NIR-fluorophore, with specific binding capacity for integrins (αvβ3, αvβ5, αvβ6) which are overexpressed on tumor cells and tumor-associated vascular endothelium associated with neoangiogenesis.

开始日期2022-11-09

申办/合作机构

Academisch Ziekenhuis Leiden

NCT04191460 / Recruiting临床2期IIT

Guided by Light: Optimizing Surgical Excision of Oral Cancer Using Real-time Fluorescence Imaging

This is a two-staged clinical trial to investigate the feasibility of intraoperative Fluorescence Imaging (FLI) to adequately assess tumor margins in patients with oral cancer using cRGD-ZW800-1.

开始日期2022-07-12

申办/合作机构

Erasmus MC

100 项与 cRGD-ZW800-1 相关的临床结果

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100 项与 cRGD-ZW800-1 相关的转化医学

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100 项与 cRGD-ZW800-1 相关的专利（医药）

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5

项与 cRGD-ZW800-1 相关的文献（医药）

2021-09-01·Clinical Cancer Research

NIR Fluorescence Imaging of Colon Cancer With cRGD-ZW800-1—Response

Letter

作者: Vahrmeijer, Alexander L. ; Sier, Cornelis F.M.

We thank Kossatz and Notni for their interest in our article about the use of fluorescent cRGD-ZW800-1 for visualization of tumor tissue in humans during surgery ([1][1]). Their concern seems the specificity of the tracer for integrin αvβ6, which is lower than for αvβ3, and the relation with our

2020-08-01·Clinical Cancer Research1区 · 医学

First-in-Human Assessment of cRGD-ZW800-1, a Zwitterionic, Integrin-Targeted, Near-Infrared Fluorescent Peptide in Colon Carcinoma

1区 · 医学

Article

作者: Vahrmeijer, Alexander L. ; Bijlstra, Okker D. ; Terwisscha van Scheltinga, Anton G.T. ; Holman, Fabian A. ; Deken, Marion M. ; Valentijn, A. Rob P.M. ; Hilling, Denise E. ; Bhairosingh, Shadhvi S. ; Handgraaf, Henricus J.M. ; Vuijk, Jaap ; van Esdonk, Michiel J. ; Burggraaf, Jacobus ; de Valk, Kim S. ; Frangioni, John V. ; Mieog, J. Sven D. ; March, Taryn L. ; Peeters, Koen C.M.J.

AbstractPurpose:Incomplete oncologic resections and damage to vital structures during colorectal cancer surgery increases morbidity and mortality. Moreover, neoadjuvant chemoradiotherapy has become the standard treatment modality for locally advanced rectal cancer, where subsequent downstaging can make identification of the primary tumor more challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by providing real-time visualization of tumors and vital structures during surgery.Experimental Design:We present the first-in-human clinical experience of a novel NIR fluorescent peptide, cRGD-ZW800-1, for the detection of colon cancer. cRGD-ZW800-1 was engineered to have an overall zwitterionic chemical structure and neutral charge to lower nonspecific uptake and thus background fluorescent signal. We performed a phase I study in 11 healthy volunteer as well as a phase II feasibility study in 12 patients undergoing an elective colon resection, assessing 0.005, 0.015, and 0.05 mg/kg cRGD-ZW800-1 for the intraoperative visualization of colon cancer.Results:cRGD-ZW800-1 appears safe, and exhibited rapid elimination into urine after a single low intravenous dose. Minimal invasive intraoperative visualization of colon cancer through full-thickness bowel wall was possible after an intravenous bolus injection of 0.05 mg/kg at least 2 hours prior to surgery. Longer intervals between injection and imaging improved the tumor-to-background ratio.Conclusions:cRGD-ZW800-1 enabled fluorescence imaging of colon cancer in both open and minimal invasive surgeries. Further development of cRGD-ZW800-1 for widespread use in cancer surgery may be warranted given the ubiquitous overexpression of various integrins on different types of tumors and their vasculature.

2017-03-28·Oncotarget

Real-time near-infrared fluorescence imaging using cRGD-ZW800-1 for intraoperative visualization of multiple cancer types

Article

作者: Prevoo, Hendrica A.J.M. ; Burggraaf, Jacobus ; van de Velde, Cornelis J.H. ; Sibinga Mulder, Babs G. ; Boogerd, Leonora S.F. ; Frangioni, John V. ; Valentijn, A. Rob P.M. ; Sier, Cornelis F.M. ; Bordo, Mark W. ; Handgraaf, Henricus J.M. ; Boonstra, Martin C. ; Vinkenburg-van Slooten, Maaike L. ; Vahrmeijer, Alexander L. ; Kuil, Joeri

Incomplete resections and damage to critical structures increase morbidity and mortality of patients with cancer. Targeted intraoperative fluorescence imaging aids surgeons by providing real-time visualization of tumors and vital structures. This study evaluated the tumor-targeted zwitterionic near-infrared fluorescent peptide cRGD-ZW800-1 as tracer for intraoperative imaging of multiple cancer types. cRGD-ZW800-1 was validated in vitro on glioblastoma (U-87 MG) and colorectal (HT-29) cell lines. Subsequently, the tracer was tested in orthotopic mouse models with HT-29, breast (MCF-7), pancreatic (BxPC-3), and oral (OSC-19) tumors. Dose-ranging studies, including doses of 0.25, 1.0, 10, and 30 nmol, in xenograft tumor models suggest an optimal dose of 10 nmol, corresponding to a human equivalent dose of 63 μg/kg, and an optimal imaging window between 2 and 24 h post-injection. The mean half-life of cRGD-ZW800-1 in blood was 25 min. Biodistribution at 4 h showed the highest fluorescence signals in tumors and kidneys. In vitro and in vivo competition experiments showed significantly lower fluorescence signals when U-87 MG cells (minus 36%, p = 0.02) or HT-29 tumor bearing mice (TBR at 4 h 3.2 ± 0.5 vs 1.8 ± 0.4, p = 0.03) were simultaneously treated with unlabeled cRGD. cRGD-ZW800-1 visualized in vivo all colorectal, breast, pancreatic, and oral tumor xenografts in mice. Screening for off-target interactions, cRGD-ZW800-1 showed only inhibition of COX-2, likely due to binding of cRGD-ZW800-1 to integrin αVβ3. Due to its recognition of various integrins, which are expressed on malignant and neoangiogenic cells, it is expected that cRGD-ZW800-1 will provide a sensitive and generic tool to visualize cancer during surgery.

100 项与 cRGD-ZW800-1 相关的药物交易

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