Delving into the Latest Updates on Delcasertib with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Delcasertib acetate (USAN)

+ [2]

Target

PKCδ

Action

inhibitors

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.

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC120H199N45O34S2

InChIKeyXPXZTVWPRKJTAA-PJKOMPQUSA-N

CAS Registry949100-39-4

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-AT

/ 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 Date21 Apr 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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15

Literatures (Medical) associated with Delcasertib

01 Jan 2025·Journal of Allergy and Clinical Immunology

Allergen-induced activation of epithelial P2Y2 receptors promotes adenosine triphosphate exocytosis and type 2 immunity in airways

Article

Author: Tojima, Ichiro ; Iijima, Koji ; O'Grady, Scott M ; Kita, Hirohito ; Srisomboon, Yotesawee

BACKGROUNDEnvironmental allergens induce the release of danger signals from the airway epithelium that trigger type 2 immune responses and promote airway inflammation.OBJECTIVEWe investigated the role of allergen-stimulated P2Y₂ receptor activation in regulating adenosine triphosphate (ATP), IL-33, and DNA release by human bronchial epithelial (hBE) cells and mouse airways.METHODSThe hBE cells were exposed to Alternaria alternata extract and secretion of ATP, IL-33, and DNA were studied in vitro. Molecular and cellular mechanisms were examined by biochemical and genetic approaches. Mice were treated intranasally with pharmacologic agents and exposed to Alternaria extract.RESULTSExposure of hBE cells to Alternaria extract stimulated P2Y₂ receptors coupled to phospholipase C β₃, leading to activation of multiple protein kinase C (PKC) isoforms and an increase in intracellular Ca²⁺ concentration. Small interfering RNAs targeting PKC δ or inhibiting PKC δ activity with delcasertib blocked exocytosis of ATP and reduced IL-33 and DNA secretion. Moreover, a peptide antagonist for myristoylated alanine-rich C-kinase substrate (MARCKS) reduced vesicular ATP release. A proximity ligand assay showed that Alternaria extract stimulated MARCKS desorption from the plasma membrane and delcasertib prevented the response. Finally, the P2Y₂ receptor antagonist AR-C118925XX and delcasertib blocked IL-33, DNA, and type 2 cytokine secretion in vivo in mice exposed to Alternaria.CONCLUSIONP2Y₂ receptor stimulation after allergen exposure promoted activation of PLC β₃, PKC δ, and MARCKS protein desorption from the apical membrane, which facilitated ATP exocytosis and subsequent secretion of IL-33 and DNA. Epithelial P2Y₂ receptors serve as primary sensors for aeroallergen-induced alarmin release by airway epithelial cells.

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.

18 May 2016·Bioconjugate ChemistryQ2 · CHEMISTRY

Biotechnology Based Process for Production of a Disulfide-Bridged Peptide

Q2 · CHEMISTRY

Article

Author: Ding, Wei ; Bryson, James W. ; Goswami, Animesh ; Witmer, Mark ; de Mas, Nuria ; Ramirez, Antonio ; Johnston, Robert M. ; Doyle, Richard ; Lo, Ehrlic ; Wan, Changhong ; Goldberg, Steven L. ; Gao, Mian ; Kim, Yeoun jin ; Hanson, Ronald L. ; Calambur, Deepa ; Chan, Yeung ; Chan, Steven H. ; Lyngberg, Olav K. ; Krystek, Stanley R.

A disulfide-bridged peptide drug development candidate contained two oligopeptide chains with 11 and 12 natural amino acids joined by a disulfide bond at the N-terminal end. An efficient biotechnology based process for the production of the disulfide-bridged peptide was developed. Initially, the two individual oligopeptide chains were prepared separately by designing different fusion proteins and expressing them in recombinant E. coli. Enzymatic or chemical cleavage of the two fusion proteins provided the two individual oligopeptide chains which could be conjugated via disulfide bond by conventional chemical reaction to the disulfide-bridged peptide. A novel heterodimeric system to bring the two oligopeptide chains closer and induce disulfide bond formation was designed by taking advantage of the self-assembly of a leucine zipper system. The heterodimeric approach involved designing fusion proteins with the acidic and basic components of the leucine zipper, additional amino acids to optimize interaction between the individual chains, specific cleavage sites, specific tag to ensure separation, and two individual oligopeptide chains. Computer modeling was used to identify the nature and number of amino acid residue to be inserted between the leucine zipper and oligopeptides for optimum interaction. Cloning and expression in rec E. coli, fermentation, followed by cell disruption resulted in the formation of heterodimeric protein with the interchain disulfide bond. Separation of the desired heterodimeric protein, followed by specific cleavage at methionine by cyanogen bromide provided the disulfide-bridged peptide.

1

News (Medical) associated with Delcasertib

07 Feb 2008

·www.biospace.com

Novel Compound May Lessen Heart Attack Damage

DURHAM, NC – A novel drug designed to lessen muscle damage from a heart attack has passed initial safety tests at the Duke Clinical Research Institute. Results of the study, available online and to be published in the February 19 issue of the journal Circulation, reflect the first time the drug has been tested in humans. The drug, known as KAI-9803, blocks the activity of an enzyme called delta protein kinase C that triggers cell and tissue death in the aftermath of percutaneous coronary intervention, or PCI. PCI is a set of procedures including balloon angioplasty and stent placement that clear and prop open clogged coronary blood vessels that lead to a heart attack – a process known as reperfusion.

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
Acute myocardial infarction	Phase 2	Poland	KAI Pharmaceuticals, Inc.	01 Nov 2008
Acute myocardial infarction	Phase 2	Finland	KAI Pharmaceuticals, Inc.	01 Nov 2008
Acute myocardial infarction	Phase 2	Spain	KAI Pharmaceuticals, Inc.	01 Nov 2008
Acute myocardial infarction	Phase 2	Netherlands	KAI Pharmaceuticals, Inc.	01 Nov 2008
Acute myocardial infarction	Phase 2	United States	KAI Pharmaceuticals, Inc.	01 Nov 2008
Acute myocardial infarction	Phase 2	Germany	KAI Pharmaceuticals, Inc.	01 Nov 2008
Acute myocardial infarction	Phase 2	New Zealand	KAI Pharmaceuticals, Inc.	01 Nov 2008
Acute myocardial infarction	Phase 2	Czechia	KAI Pharmaceuticals, Inc.	01 Nov 2008
Acute myocardial infarction	Phase 2	Australia	KAI Pharmaceuticals, Inc.	01 Nov 2008
Acute myocardial infarction	Phase 2	Sweden	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	iodoyrsjjk(yxqsqqimxd) = vdkwwsaxiv yymubqsmrl (jaydfpirxc )	Negative	01 Oct 2014
				Delcasertib 50 mg/h	iodoyrsjjk(yxqsqqimxd) = iivmpswowp yymubqsmrl (jaydfpirxc )

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Biosimilar

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

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Delcasertib

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation