Nastorazepide Calcium(Nastorazepide Calcium) - 药物靶点：CCKB_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

CCKB

作用机制

CCKB拮抗剂(胆囊收缩素B受体拮抗剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病

在研适应症-

非在研适应症

转移性胰腺腺癌不能切除性胰腺癌

原研机构

Zeria Pharmaceutical Co., Ltd.

在研机构-

非在研机构

Zeria Pharmaceutical Co., Ltd.

最高研发阶段无进展临床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C29H36N4O5

InChIKeyVIJCCFFEBCOOIE-JOCHJYFZSA-N

CAS号209219-38-5

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关联

4

项与 Nastorazepide Calcium 相关的临床试验

NCT02117258 / Completed临床2期

Randomized Phase II Study of Gemcitabine Plus Z-360 in Metastatic Pancreatic Adenocarcinoma Compared With Gemcitabine Plus Placebo ( ZIPANG Study )

The primary objective of this study is to compare the efficacy of GEM plus Z-360 versus GEM plus placebo on the overall survival (OS) in subjects with metastatic Pancreatic Adenocarcinoma.

开始日期2014-04-01

申办/合作机构

Zeria Pharmaceutical Co., Ltd.

NCT01776463 / Completed临床1期

A Single Centre, Randomized, Double-blind, Ascending Dose, Placebo-controlled, and Food Effect Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of Z-360 and Placebo in Healthy Subjects

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (including food effect) of single and multiple doses of Z-360 in healthy Japanese subjects.

开始日期2013-01-01

申办/合作机构

Zeria Pharmaceutical Co., Ltd.

NCT00288925 / Completed临床1/2期

Phase Ib/IIa, to Evaluate the Safety and Pharmacokinetics of Z-360 in Subjects With Unresectable Advanced Pancreatic Cancer in Combination With Gemcitabine Treatment

To evaluate the safety of two doses of Z-360 with Gemcitabine administration for subjects with unresectable advanced pancreatic cancer in order to determine the optimal dosage for PhaseII study

开始日期2005-09-01

申办/合作机构

Zeria Pharmaceutical Co., Ltd.

100 项与 Nastorazepide Calcium 相关的临床结果

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100 项与 Nastorazepide Calcium 相关的转化医学

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100 项与 Nastorazepide Calcium 相关的专利（医药）

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17

项与 Nastorazepide Calcium 相关的文献（医药）

2024-08-05·Molecular Pharmaceutics

Development and Validation of Novel Z-360-Based Macromolecules for the Active Targeting of CCK2-R

Article

作者: Bisio, Alessandra ; Spessot, Eugenia ; Mastrotto, Francesca ; Croci, Stefania ; Bellio, Greta ; Verona, Marco ; Andrighetto, Alberto ; Vettorato, Elisa ; Maniglio, Devid ; Marzaro, Giovanni ; Asti, Mattia ; Filadi, Riccardo

The cholecystokinin type 2 receptor (CCK2-R) represents an ideal target for cancer therapy since it is overexpressed in several tumors and is associated with poor prognosis. Nastorazepide (Z-360), a selective CCK2-R antagonist, has been widely investigated as a CCK2-R ligand for targeted therapy; however, its high hydrophobicity may represent a limit to cell selectivity and optimal in vivo biodistribution. Here, we present three new fluorescent Z-360 derivatives (IP-002_G-Rho, IP-002_L-Rho, and IP-002_M-Rho) in which nastorazepide was linked, through spacers bearing different saccharides (glucose (G), lactose (L), and maltotriose (M)), to sulforhodamine B. A fourth compound (IP-002_H-Rho) with no pendant sugar was also synthesized as a control. Through two-dimensional (2D) and three-dimensional (3D) in vitro studies, we evaluated the compound association with and selectivity for CCK2-R-overexpressing cells (A431-CCK2-R⁺) vs CCK2-R-underexpressing cells (A431 WT). 2D in vitro studies highlighted a progressive increase of IP-002_x-Rho association with A431-CCK2-R⁺ cells according to the linker hydrophilicity, that is, maltotriose > lactose > glucose > hydrogen, with IP-002_M-Rho showing a 2.4- and a 1.36-fold higher uptake than IP-002_G-Rho and IP-002_L-Rho, respectively. Unexpectedly, IP-002_H-Rho showed a similar cell association to that of IP-002_L-Rho but with no difference between the two tested cell lines. On the contrary, association with A431-CCK2-R⁺ cells as compared to the A431 WT was found to be 1.08-, 1.14-, and 1.37-fold higher for IP-002_G-Rho, IP-002_L-Rho, and IP-002_M-Rho, respectively, proving IP-002_M-Rho to be the best-performing compound, as also confirmed by competition studies. Trafficking studies on A431-CCK2-R⁺ cells incubated with IP-002_M-Rho suggested the coexistence of receptor-mediated endocytosis and simple diffusion. On the contrary, a high and selective uptake of IP-002_M-Rho by A431-CCK2-R⁺ cells only was observed on 3D scaffolds embedded with cells, underlining the importance of 3D models in in vitro preliminary evaluation.

2021-01-08·ChemMedChem

Radiolabelled CCK₂R Antagonists Containing PEG Linkers: Design, Synthesis and Evaluation

Article

作者: Kolenc Peitl, Petra ; Tomašič, Tihomir ; Krošelj, Marko ; Novak, Doroteja ; Plavec, Janez ; Anderluh, Marko ; Javornik, Uroš

AbstractThe cholecystokinin‐2/gastrin receptor (CCK2R) is considered a suitable target for the development of radiolabelled antagonists, due to its overexpression in various tumours, but no such compounds are available in clinical use. Therefore, we designed novel 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid‐conjugated ligands based on CCK2R antagonist Z360/nastorazepide. As a proof of concept that CCK2R antagonistic activity can be retained by extending the Z360/nastorazepide structure using suitable linker, we present herein three compounds containing various PEG linkers synthesised on solid phase and in solution. The antagonistic properties were measured in a functional assay in the A431‐CCK2R cell line (in the presence of agonist G17), with IC50 values of 3.31, 4.11 and 10.4 nM for compounds containing PEG4, PEG6 and PEG12, respectively. All compounds were successfully radiolabelled with indium‐111, lutetium‐177 and gallium‐68 (incorporation of radiometal >95 %). The gallium‐68‐labelled compounds were stable for up to 2 h (PBS, 37 °C). log D7.4 values were determined for indium‐111‐ and gallium‐68‐labelled compounds, showing improved hydrophilicity compared to the reference compound.

2020-08-03·Molecular Pharmaceutics2区 · 医学

[^99mTc]Tc-DGA1, a Promising CCK₂R-Antagonist-Based Tracer for Tumor Diagnosis with Single-Photon Emission Computed Tomography

2区 · 医学

Article

作者: Radolf, Thorsten ; Andreae, Fritz ; Holz, George G. ; Kanellopoulos, Panagiotis ; Rouchota, Maritina ; Loudos, George ; Kaloudi, Aikaterini ; Nock, Berthold Artur ; Maina, Theodosia ; Chepurny, Oleg G.

Radiolabeled gastrin analogues have been proposed for theranostics of cholecystokinin subtype 2 receptor (CCK₂R)-positive cancer. Peptide radioligands based on other receptor antagonists have displayed superior pharmacokinetics and higher biosafety than agonists. Here, we present DGA1, a derivative of the nonpeptidic CCK₂R antagonist Z-360 carrying an acyclic tetraamine, for [^99mTc]Tc labeling. Preclinical comparison of [^99mTc]Tc-DGA1 with [^99mTc]Tc-DG2 (CCK₂R-agonist reference) was conducted in HEK293-CCK₂R/CCK_2i4svR cells and mice models, qualifying [^99mTc]Tc-DGA1 for further study in patients with CCK₂R-positive tumors and single-photon emission computed tomography/CT.

100 项与 Nastorazepide Calcium 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
转移性胰腺腺癌	临床2期	中国台湾	Zeria Pharmaceutical Co., Ltd.	2014-04-01
转移性胰腺腺癌	临床2期	韩国	Zeria Pharmaceutical Co., Ltd.	2014-04-01
不能切除性胰腺癌	临床2期	英国	Zeria Pharmaceutical Co., Ltd.	2005-09-01
转移性胰腺腺癌	药物发现	日本	Zeria Pharmaceutical Co., Ltd.	2014-04-01

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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


NCT02117258 (Pubmed \| Cancer Chemother Pharmacol) 人工标引	临床2期	胰腺继发性恶性肿瘤	167	gemcitabine+Z-360	(繭蓋餘繭醖觸觸構製鬱) = 範製網獵簾餘鏇網鏇餘鑰簾積繭顧觸醖製憲積 (鹽顧範餘壓醖壓鑰艱構 )	积极	2017-08-01
				gemcitabine+Placebo	(繭蓋餘繭醖觸觸構製鬱) = 獵醖憲鬱選膚積顧遞蓋鑰簾積繭顧觸醖製憲積 (鹽顧範餘壓醖壓鑰艱構 )
ASCO2008	临床1/2期	不能切除性胰腺癌	-	Z-360 120mg	(衊膚窪窪鑰餘遞簾窪膚) = 夢鏇壓衊網夢鹹襯簾鑰夢憲積壓範範憲憲壓遞 (製繭餘蓋艱膚構簾網範 )	-	2008-05-20
				Z-360 240mg	(衊膚窪窪鑰餘遞簾窪膚) = 糧築襯鏇選簾淵夢遞夢夢憲積壓範範憲憲壓遞 (製繭餘蓋艱膚構簾網範 )