Delving into the Latest Updates on PZ-128 with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms-

Target

PAR-1

Mechanism

F2R antagonists(Protease-activated receptor-1 antagonists)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Thrombosis

Inactive Indication

Acute Coronary SyndromeCoronary Artery Disease

Originator Organization

Tufts Medical Center, Inc.

Active Organization

Tufts Medical Center, Inc.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC55H99N13O9

InChIKeyVZRIKWNVDCTBTF-BKGFHLQYSA-N

CAS Registry371131-16-7

Gene Sequence

Sequence Code 9462645

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.

Start Date27 May 2016

Sponsor / Collaborator

Tufts Medical Center, Inc.

[+3]

NCT01806077 / CompletedPhase 1IIT

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.

Start Date01 Apr 2013

Sponsor / Collaborator

Tufts Medical Center, Inc.

[+2]

100 Clinical Results associated with PZ-128

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100 Translational Medicine associated with PZ-128

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100 Patents (Medical) associated with PZ-128

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10

Literatures (Medical) associated with PZ-128

01 Oct 2023·Circulation: Heart Failure

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

Article

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

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 weeksRESULTS: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.

01 Jan 2022·Methods in Molecular Biology

Lipopeptide Pepducins as Therapeutic Agents

Article

Author: Michael, Emily ; Covic, Lidija ; Kuliopulos, Athan

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.

17 Dec 2021·The Journal of Organic ChemistryQ2 · CHEMISTRY

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

Q2 · CHEMISTRY

Article

Author: Madhavan, Nandita ; Bisht, Babita

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 Deals associated with PZ-128

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11839

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Thrombosis	Phase 2	-	Tufts Medical Center, Inc.	-
Acute Coronary Syndrome	Phase 1	US	Tufts Medical Center, Inc.	27 May 2016
Coronary Artery Disease	Phase 1	US	Tufts Medical Center, Inc.	27 May 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02561000 (TRIP-PCI, CTgov)	Phase 2	Acute Coronary Syndrome \| Coronary Artery Disease	100	Placebo (Placebo)	ukxqsovxqo(awomecottb) = xclxlpskfi oafjbrfeum (duzwqpoybt, epegguvwvt - teiuyvksdr) View more	-	09 Mar 2021
				PZ-128 (PZ-128 0.3 mg/kg)	ukxqsovxqo(awomecottb) = ukarwaaqqe oafjbrfeum (duzwqpoybt, kteabavswg - whxwqdjoox) View more