Delcasertib(Delcasertib) - 药物靶点：PKCδ_专利_临床

概要

基本信息

药物类型

合成多肽

别名

Delcasertib acetate (USAN)

+ [2]

靶点

PKCδ

作用机制

PKCδ抑制剂(蛋白激酶C-δ抑制剂)

治疗领域

心血管疾病其他疾病

在研适应症-

非在研适应症

急性心肌梗塞梗塞ST段抬高心肌梗死

原研机构

Amgen, Inc.

在研机构-

非在研机构

KAI Pharmaceuticals, Inc.

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C120H199N45O34S2

InChIKeyXPXZTVWPRKJTAA-PJKOMPQUSA-N

CAS号949100-39-4

序列信息

Sequence Code 29414

来源: *****

Sequence Code 57106

来源: *****

关联

3

项与 Delcasertib 相关的临床试验

NCT00785954 / Completed临床2期

Inhibition of Delta-protein Kinase C for the Reduction of Infarct Size in Acute Myocardial Infarction

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.

开始日期2008-11-01

申办/合作机构

KAI Pharmaceuticals, Inc.

[+3]

EUCTR2004-005252-14-CZ / Not yet recruitingN/A

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

开始日期2005-05-23

申办/合作机构

KAI Pharmaceuticals, Inc.

NCT00093197 / Completed临床1/2期

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.

开始日期2004-09-01

申办/合作机构

KAI Pharmaceuticals, Inc.

100 项与 Delcasertib 相关的临床结果

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100 项与 Delcasertib 相关的转化医学

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100 项与 Delcasertib 相关的专利（医药）

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11

项与 Delcasertib 相关的文献（医药）

2020-03-01·Journal of Cellular and Molecular Medicine2区 · 医学

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

2区 · 医学

ReviewOA

作者: 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.

2014-10-01·European Heart Journal

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

Communications

作者: 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

2014-10-01·European Heart Journal1区 · 医学

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区 · 医学

Article

作者: 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 ; Galla, John ; Krucoff, Mitchell ; Brennan, Danielle ; Mehta, Shamir ; 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 项与 Delcasertib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10457	-	-	DB05560

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
梗塞	临床2期	西班牙	KAI Pharmaceuticals, Inc.	2008-11-01
梗塞	临床2期	波兰	KAI Pharmaceuticals, Inc.	2008-11-01
梗塞	临床2期	丹麦	KAI Pharmaceuticals, Inc.	2008-11-01
梗塞	临床2期	匈牙利	KAI Pharmaceuticals, Inc.	2008-11-01
梗塞	临床2期	澳大利亚	KAI Pharmaceuticals, Inc.	2008-11-01
梗塞	临床2期	比利时	KAI Pharmaceuticals, Inc.	2008-11-01
梗塞	临床2期	加拿大	KAI Pharmaceuticals, Inc.	2008-11-01
梗塞	临床2期	美国	KAI Pharmaceuticals, Inc.	2008-11-01
梗塞	临床2期	荷兰	KAI Pharmaceuticals, Inc.	2008-11-01
梗塞	临床2期	意大利	KAI Pharmaceuticals, Inc.	2008-11-01

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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


NCT00785954 (PROTECTION AMI, Pubmed \| Eur Heart J)	临床2期	ST段抬高心肌梗死	1,010	Placebo	醖齋襯廠鬱艱願願鏇齋(艱鹹壓願鬱窪築廠齋鬱) = 遞簾餘壓鏇鑰願糧艱鹽鑰廠夢窪襯範製築淵淵 (醖壓壓糧艱鏇餘壓選夢 )	不佳	2014-10-01
				Delcasertib 50 mg/h	醖齋襯廠鬱艱願願鏇齋(艱鹹壓願鬱窪築廠齋鬱) = 鹽積觸鬱夢糧衊鹽鏇鑰鑰廠夢窪襯範製築淵淵 (醖壓壓糧艱鏇餘壓選夢 )