Delving into the Latest Updates on Delcasertib with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Delcasertib acetate (USAN)

+ [2]

Target

PKCδ

Mechanism

PKCδ inhibitors(Protein kinase C delta inhibitors)

Therapeutic Areas

Cardiovascular DiseasesOther Diseases

Active Indication-

Inactive Indication

Acute myocardial infarctionInfarctionST Elevation Myocardial Infarction

Originator Organization

Amgen, Inc.

Active Organization-

Inactive Organization

KAI Pharmaceuticals, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC120H199N45O34S2

InChIKeyXPXZTVWPRKJTAA-PJKOMPQUSA-N

CAS Registry949100-39-4

Gene Sequence

Sequence Code 29414

Source: *****

Sequence Code 57106

Source: *****

The purpose of this study is to determine whether KAI-9803 is safe and effective in reducing infarct size in subjects with ST elevation myocardial infarction (heart attack) undergoing a percutaneous coronary intervention (PCI). A select number of sites will also participate in a substudy where eligible patients will undergo an additional procedure;cardiac magnetic resonance imaging.

Start Date01 Nov 2008

Sponsor / Collaborator

KAI Pharmaceuticals, Inc.

[+3]

EUCTR2004-005252-14-CZ / Not yet recruitingNot Applicable

Direct Inhibition of d Protein Kinase C Enzyme to Limit Total Infarct Size in Acute Myocardial Infarction (DELTA MI): Intracoronary KAI-9803 for Injection as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST Elevation Myocardial Infarction - DELTA MI

Start Date23 May 2005

Sponsor / Collaborator

KAI Pharmaceuticals, Inc.

NCT00093197 / CompletedPhase 1/2

Intracoronary KAI-9803 for Injection as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Elevation Myocardial Infarction

Restoring blood flow to coronary arteries as quickly as possible is the best way to reduce the damage to the muscle that occurs with a heart attack. However, up to 25-50% of patients who have angioplasty may have ongoing damage to the heart muscle when the blockage is opened and blood flow is restored. Complications which may result from this ongoing damage include a larger area of damaged muscle in the heart, enlargement of the heart, an increased risk of death, and an increased risk of heart failure. Some of the ongoing damage may involve increased levels of the protein kinase C (PKC) enzyme. KAI-9803 is a selective inhibitor of delta PKC. In this study, delta PKC is used with angioplasty and other standard procedures to restore blood flow after a heart attack. This study is designed to evaluate safety of different amounts of KAI-9803 when used in treating heart attack patients undergoing angioplasty. We will also try to evaluate whether KAI-9803 can reduce the amount of heart muscle damage and the complications that may occur in these patients.

Start Date01 Sep 2004

Sponsor / Collaborator

KAI Pharmaceuticals, Inc.

100 Clinical Results associated with Delcasertib

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100 Translational Medicine associated with Delcasertib

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100 Patents (Medical) associated with Delcasertib

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11

Literatures (Medical) associated with Delcasertib

01 Mar 2020·Journal of Cellular and Molecular MedicineQ2 · MEDICINE

Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST‐segment elevation myocardial infarction

Q2 · MEDICINE

ReviewOA

Author: Ruiz‐Meana, Marisol ; Cabrera‐Fuentes, Hector Alejandro ; Bøtker, Hans Erik ; Heusch, Gerd ; Ovize, Michel

AbstractPre‐clinical studies have indicated that mitoprotective drugs may add cardioprotection beyond rapid revascularization, antiplatelet therapy and risk modification. We review the clinical efficacy of mitoprotective drugs that have progressed to clinical testing comprising cyclosporine A, KAI‐9803, MTP131 and TRO 40303. Whereas cyclosporine may reduce infarct size in patients undergoing primary angioplasty as evaluated by release of myocardial ischaemic biomarkers and infarct size imaging, the other drugs were not capable of demonstrating this effect in the clinical setting. The absent effect leaves the role of the mitochondrial permeability transition pore for reperfusion injury in humans unanswered and indicates that targeting one single mechanism to provide mitoprotection may not be efficient. Moreover, the lack of effect may relate to favourable outcome with current optimal therapy, but conditions such as age, sex, diabetes, dyslipidaemia and concurrent medications may also alter mitochondrial function. However, as long as the molecular structure of the pore remains unknown and specific inhibitors of its opening are lacking, the mitochondrial permeability transition pore remains a target for alleviation of reperfusion injury. Nevertheless, taking conditions such as ageing, sex, comorbidities and co‐medication into account may be of paramount importance during the design of pre‐clinical and clinical studies testing mitoprotective drugs.

01 Oct 2014·European Heart Journal

Ameliorating reperfusion injury in STEMI: dead or alive?: Figure 1

Communications

Author: Bainey, Kevin R ; Armstrong, Paul W

This editorial refers to ‘Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial’[†][1], by A.M. Lincoff et al. , on page 2516 Reperfusion therapy reduces infarct size and improves left ventricular function in ST-segement elevation myocardial infarction (STEMI). Despite restoration of epicardial perfusion and commensurate reductions in morbidity and mortality, residual hazard persists. Restoration of coronary blood flow after prolonged ischaemia may exhibit a ‘double edge’ characterized as reperfusion injury with resulting cell death that can account for up to half of the final infarct size.1 The pathophysiology of reperfusion injury is probably multifactorial and includes distal embolization/platelet plugging of the microvasculature, release of toxic inflammatory mediators, production of oxygen free radicals, and accumulation of intracellular calcium. Whereas various cytoprotective agents have shown promise in animal models, to date translation of this benefit has been disappointing at best.2 Hence, combating reperfusion injury remains one of the final therapeutic frontiers in STEMI management. Because protein kinase C (PKC) isoenzymes modulate myocardial protection, their potential for therapeutic intervention has been of interest.3,4 However, counter-regulatory cardioprotective activity has been reported with specific PKC isoenzymes. This ‘ying–yang’ counterpoint is represented by activation of ePKC which provides cardioprotection whereas activation of δPKC induces myocardial cell damage following ischaemia.5 Application of this pathway to myocardial protection led to the development of the selective δPKC antagonist, delcasertib, which reduced infarct size and improved microvascular function following reperfusion in animal models.6,7 Given the experimental promise of delcasertib, a phase II dose-escalation study of 154 patients … [1]: #fn-2

01 Oct 2014·European Heart JournalQ1 · MEDICINE

Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial

Q1 · MEDICINE

Article

Author: Zelizko, Michael ; Rynkiewicz, Andrzej ; Radke, Peter ; Fernandez-Ortiz, Antonio ; Lincoff, A Michael ; White, Harvey ; Jensen, Svend Eggert ; Dos Santos Ferreira, Jorge Manuel ; Bell, Gregory ; Roe, Matthew ; Goodman, Shaun ; Laine, Mika ; Guetta, Victor ; Atar, Dan ; Aylward, Philip ; Belli, Guido ; Forster, Tamas ; Kleiman, Neal ; Krucoff, Mitchell ; Mehta, Shamir ; Galla, John ; Brennan, Danielle ; Erlinge, David ; Schoors, Danny ; McErlean, Ellen ; Suryapranata, Harry

AIMSDelcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI).METHODS AND RESULTSA multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed.CONCLUSIONSSelective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.

100 Deals associated with Delcasertib

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External Link

KEGG	Wiki	ATC	Drug Bank
D10457	-	-	DB05560

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Infarction	Phase 2	NZ	KAI Pharmaceuticals, Inc.	01 Nov 2008
Infarction	Phase 2	HU	KAI Pharmaceuticals, Inc.	01 Nov 2008
Infarction	Phase 2	AU	KAI Pharmaceuticals, Inc.	01 Nov 2008
Infarction	Phase 2	DE	KAI Pharmaceuticals, Inc.	01 Nov 2008
Infarction	Phase 2	IL	KAI Pharmaceuticals, Inc.	01 Nov 2008
Infarction	Phase 2	US	KAI Pharmaceuticals, Inc.	01 Nov 2008
Infarction	Phase 2	NL	KAI Pharmaceuticals, Inc.	01 Nov 2008
Infarction	Phase 2	NO	KAI Pharmaceuticals, Inc.	01 Nov 2008
Infarction	Phase 1	FI	KAI Pharmaceuticals, Inc.	01 Nov 2008
Infarction	Phase 1	CZ	KAI Pharmaceuticals, Inc.	01 Nov 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00785954 (PROTECTION AMI, Pubmed \| Eur Heart J)	Phase 2	ST Elevation Myocardial Infarction	1,010	Placebo	vsjyozqskm(iacasxvsna) = ptjvpfmotv trctudoljj (fanspcvxvc )	Negative	01 Oct 2014
				Delcasertib 50 mg/h	vsjyozqskm(iacasxvsna) = roimetufgn trctudoljj (fanspcvxvc )