(PZ-128) - 药物靶点：PAR-1_在研适应症：血栓形成_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

PAR-1

作用机制

F2R拮抗剂(蛋白酶活化受体1拮抗剂)

治疗领域

心血管疾病

在研适应症

血栓形成

非在研适应症-

原研机构

Tufts Medical Center, Inc.

在研机构

Tufts Medical Center, Inc.

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-

结构

分子式C55H99N13O9

InChIKeyVZRIKWNVDCTBTF-BKGFHLQYSA-N

CAS号371131-16-7

序列信息

Sequence Code 9462645

关联

2

项与 PZ-128 相关的临床试验

NCT02561000 / Completed临床2期IIT

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of PZ-128 in Subjects Undergoing Non-Emergent Percutaneous Coronary Intervention- Thrombin Receptor Inhibitory Pepducin in PCI (TRIP-PCI)

The object of the study is to determine whether different doses of PZ-128, when added to standard medical care in persons undergoing cardiac catheterization/percutaneous coronary intervention, will increase the risk of bleeding.
A secondary objective is to determine whether patients treated with PZ-128 have fewer cardiac events such as heart attack, bypass surgery or stroke compared with those persons treated with the standard of care.

开始日期2016-05-27

申办/合作机构

Tufts Medical Center, Inc.

[+3]

NCT01806077 / Completed临床1期IIT

Demonstration of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Antiplatelet Effect of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors

This study is a Phase I, intravenous, single-dose escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PZ-128 (pepducin inhibitor of PAR1) in subjects with vascular disease or who have 2 or more coronary artery disease (CAD) risk factors.

开始日期2013-04-01

申办/合作机构

Tufts Medical Center, Inc.

[+2]

100 项与 PZ-128 相关的临床结果

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100 项与 PZ-128 相关的转化医学

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100 项与 PZ-128 相关的专利（医药）

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10

项与 PZ-128 相关的文献（医药）

2023-07-21·Circulation. Heart failure

Suppression of Heart Failure With PAR1 Pepducin Technology in a Pressure Overload Model in Mice.

Article

作者: Elizabeth K Fletcher ; Njabulo Ngwenyama ; Nga Nguyen ; Susan E Turner ; Lidija Covic ; Pilar Alcaide ; Athan Kuliopulos

BACKGROUND:

PAR1 (protease-activated receptor-1) contributes to acute thrombosis, but it is not clear whether the receptor is involved in deleterious inflammatory and profibrotic processes in heart failure. Here, we employ the pepducin technology to determine the effects of targeting PAR1 in a mouse heart failure with reduced ejection fraction model.

METHODS:

After undergoing transverse aortic constriction pressure overload or sham surgery, C57BL/6J mice were randomized to daily sc PZ-128 pepducin or vehicle, and cardiac function, inflammation, fibrosis, and molecular analyses conducted at 7 weeks RESULTS: After 7 weeks of transverse aortic constriction, vehicle mice had marked increases in macrophage/monocyte infiltration and fibrosis of the left ventricle as compared with Sham mice. PZ-128 treatment significantly suppressed the inflammatory cell infiltration and cardiac fibrosis. Despite no effect on myocyte cell hypertrophy, PZ-128 afforded a significant reduction in overall left ventricle weight and completely protected against the transverse aortic constriction-induced impairments in left ventricle ejection fraction. PZ-128 significantly suppressed transverse aortic constriction-induced increases in an array of genes involved in myocardial stress, fibrosis, and inflammation.

CONCLUSIONS:

The PZ-128 pepducin is highly effective in protecting against cardiac inflammation, fibrosis, and loss of left ventricle function in a mouse model.

2022-01-01·Methods in molecular biology (Clifton, N.J.)

Lipopeptide Pepducins as Therapeutic Agents.

Article

作者: Emily Michael ; Lidija Covic ; Athan Kuliopulos

Pepducins are lipidated peptides that target the intracellular loops of G protein-coupled receptors (GPCRs) in order to modulate transmembrane signaling to internally located effectors. With a wide array of potential activities ranging from partial, biased, or full agonism to antagonism, pepducins represent a versatile class of compounds that can be used to potentially treat diverse human diseases or be employed as novel tools to probe complex mechanisms of receptor activation and signaling in cells and in animals. Here, we describe a number of different pepducins including an advanced compound, PZ-128, that has successfully progressed through phase 2 clinical trials in cardiac patients demonstrating safety and efficacy in suppressing myonecrosis and arterial thrombosis.

2021-11-25·The Journal of organic chemistry2区 · 化学

Quick Access to High-Purity Peptide Drugs Bradykinin, Leuprolide Analogue, 2(PZ-128), and Rapastinel with Minimal Reagents.

2区 · 化学

Article

作者: Babita Bisht ; Nandita Madhavan

Peptide drugs bradykinin, a leuprolide analogue, 2(PZ-128), and rapastinel are synthesized in 56-77% yield using heating-assisted liquid-phase peptide synthesis on a soluble polynorbornene support. These drugs of commercial utility and complex structures are obtained in 2-5.5 h with no epimerization and >95% purity using only 1.2 equivalents of amino acids and coupling reagents. The peptide yield and purity are comparable or superior to the reported methods.

100 项与 PZ-128 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11839

研发状态

适应症	最高研发状态	国家/地区	公司
血栓形成	临床2期	-	Tufts Medical Center, Inc. 更多

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02561000 (CTgov)	临床2期	冠心病 \| 急性冠状动脉综合征	100	Placebo (Placebo)	夢獵鹽簾鹽積壓鏇糧簾(築網鬱觸夢鑰窪齋觸廠) = 鬱選遞憲鬱蓋築鑰廠襯顧蓋鏇醖憲鹹獵淵願襯 (觸積憲鑰鏇鏇齋築築襯, 膚淵鏇範製齋醖積鹽夢 ~ 簾糧鏇構夢衊願獵觸膚) 更多	-	2021-03-09
NCT02561000 (CTgov)	临床2期	冠心病 \| 急性冠状动脉综合征	100	PZ-128 (PZ-128 0.3 mg/kg)	夢獵鹽簾鹽積壓鏇糧簾(築網鬱觸夢鑰窪齋觸廠) = 壓遞憲淵窪齋繭範觸齋顧蓋鏇醖憲鹹獵淵願襯 (觸積憲鑰鏇鏇齋築築襯, 淵築簾齋窪齋鹹範範鏇 ~ 壓淵簾鬱鹽製醖衊遞醖) 更多	-	2021-03-09
NCT01806077 (Pubmed \| Transplant Proc)	临床1期	冠心病	31	PZ-128	(衊繭廠襯艱膚網繭鹽鹽) = 繭築艱艱夢鏇齋鹹鹽艱願膚膚簾製繭醖鬱鬱築 (選餘製鏇膚窪廠鹹廠蓋 )	-	2016-01-01