E-2027(E-2027) - 药物靶点：PDE9A_在研适应症：帕金森病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Irsenontrine、Irsenontrine maleate

+ [5]

靶点

PDE9A

作用方式

抑制剂

作用机制

PDE9A抑制剂(磷酸二酯酶9A抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

权益机构-

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

结构/序列

分子式C26H26N4O7

InChIKeyAFKSGMDXSLTKSU-DASCVMRKSA-N

CAS号1630083-70-3

关联

6

项与 E-2027 相关的临床试验

NCT04764669

/ Completed临床2期

An Open-Label Study To Evaluate the Pharmacodynamic Effects, Efficacy, Safety, and Tolerability of E2027 in Subjects With Dementia With Lewy Bodies or Parkinson's Disease Dementia With or Without Amyloid Copathology

The purpose of study is to demonstrate the pharmacodynamic (PD) effects of E2027 on cerebrospinal fluid (CSF) cyclic guanosine monophosphate (cGMP) in participants with DLB and PDD with and without amyloid copathology after 9 weeks of treatment.

开始日期2021-02-25

申办/合作机构

Eisai, Inc.

NCT04023877

/ Completed临床1期

An Open-Label, Single-Dose Study to Determine the Metabolism and Elimination of [14C]E2027 in Healthy Male Subjects

The primary objective of the study is to achieve mass balance recovery of [14C]-radiolabel in urine and feces and to identify and quantify the main elimination pathways of E2027.

开始日期2019-07-18

申办/合作机构

Eisai, Inc.

NCT03467152

/ Completed临床2期

A Placebo-Controlled, Double-Blind, Parallel-Group, Randomized, Study To Evaluate the Efficacy, Safety and Tolerability of E2027 in Subjects With Dementia With Lewy Bodies

This study will be conducted to compare Irsenontrine to placebo on the cognitive endpoint of Montreal Cognitive Assessment (MoCA) and the global clinical endpoint of Clinician's Interview Based Impression of Change Plus (CIBIC-Plus) Caregiver Input in participants with dementia with Lewy bodies after 12 weeks of treatment.

开始日期2018-05-04

申办/合作机构

Eisai, Inc.

100 项与 E-2027 相关的临床结果

登录后查看更多信息

100 项与 E-2027 相关的转化医学

登录后查看更多信息

100 项与 E-2027 相关的专利（医药）

登录后查看更多信息

6

项与 E-2027 相关的文献（医药）

2025-08-01·Neuropharmacology

A novel selective phosphodiesterase 9 inhibitor, irsenontrine (E2027), enhances GluA1 phosphorylation in neurons and improves learning and memory via cyclic GMP elevation

Article

作者: Ando, Mai ; Mano, Yuji ; Kotani, Sadaharu ; Ishii, Satoko ; Ishihara, Yasuharu ; Nakatani, Yosuke ; Goto, Yasuaki ; Watanabe, Naoto ; Ishikawa, Yukio ; Miyamoto, Norimasa

Phosphodiesterase 9 (PDE9) plays a critical role in synaptic plasticity and cognitive function by modulating cyclic GMP (cGMP). Many reports have shown that PDE9 inhibition improves cognitive function and synaptic plasticity in rodents. Several studies have found that the NO/cGMP/PKG pathway is downregulated in patients with Alzheimer's disease (AD) or dementia with Lewy bodies (DLB) and in older individuals. A PDE9 inhibitor could therefore be a potential therapeutic approach for improving cognitive dysfunction in dementia, including in AD and DLB. We previously discovered a novel PDE9 inhibitor, irsenontrine (E2027). In the current study, irsenontrine showed highly selective affinity for PDE9 with more than 1800-fold selectivity over other PDEs. Irsenontrine maleate significantly increased intracellular cGMP levels in rat cortical primary neurons, and phosphorylation of AMPA receptor subunit GluA1 was induced following cGMP elevation. Oral administration of irsenontrine significantly upregulated cGMP levels in the hippocampus and cerebrospinal fluid (CSF) of naïve rats, and a novel object recognition test showed that irsenontrine administration also significantly improved learning and memory. The effects of irsenontrine were confirmed in rats treated with Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME), a model of learning and memory impairment due to downregulation of the cGMP pathway. l-NAME downregulated cGMP in the CSF and hippocampus and impaired novel object recognition, but oral administration of irsenontrine clearly attenuated these phenotypes. These results indicate that irsenontrine improves learning and memory via the elevation of cGMP levels, and they strongly suggest that irsenontrine could be a novel therapeutic approach against cognitive dysfunction.

2025-06-01·Neural Regeneration Research

Phosphodiesterase 9 localization in cytoplasm and nucleus: the gateway to selective targeting in neuroprotection?

Article

作者: Anyanwu, Margrate ; Gianoncelli, Alessandra ; Giannangeli, Matteo ; Ribaudo, Giovanni

The umbrella term "neurodegenerative disorders" (NDDs) refers to several conditions characterized by a progressive loss of structure and function of cells belonging to the nervous system.Such diseases affect more than 50 million people worldwide.Neurodegenerative disorders are characterized by sundry factors and pathophysiol. mechanisms that are challenging to be fully profiled.Many of these rely on cell signaling pathways to preserve homeostasis, involving second messengers such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine 3′, 5′-monophosphate (cGMP).Their ability to control the duration and amplitude of the signaling cascade is given by the presence of several common and uncommon effectors.Protein kinases A and G (PKA and PKG), phosphodiesterases (PDEs), and scaffold proteins are among them.

2023-10-01·Current Neurology and Neuroscience Reports

Lewy Body Dementia: An Overview of Promising Therapeutics

Review

作者: Sha, Sharon J ; Skylar-Scott, Irina A

PURPOSE OF REVIEWLewy body dementia (LBD) encompasses dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). This article will emphasize potential disease-modifying therapies as well as investigative symptomatic treatments for non-motor symptoms including cognitive impairment and psychosis that can present a tremendous burden to patients with LBD and their caregivers.RECENT FINDINGSWe review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy populations (Anle138b, fosgonimeton, and CT1812). We also appraise four symptomatic therapies for cognitive impairment, but due to safety and efficacy concerns, only NYX-458 remains under active investigation. Of symptomatic therapies for psychosis recently investigated, pimavanserin shows promise in LBD, but studies of nelotanserin have been suspended. Although the discovery of novel symptomatic and disease-modifying therapeutics remains a significant challenge, recently published and upcoming trials signify promising strides toward that aim.

100 项与 E-2027 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
帕金森病	临床3期	-	Eisai Co., Ltd.	-
帕金森病所致痴呆	药物发现	加拿大	Eisai, Inc.	2021-02-25
帕金森病所致痴呆	药物发现	美国	Eisai, Inc.	2021-02-25
路易体病	药物发现	英国	Eisai, Inc.	2018-05-04
路易体病	药物发现	法国	Eisai, Inc.	2018-05-04
路易体病	药物发现	意大利	Eisai, Inc.	2018-05-04
路易体病	药物发现	西班牙	Eisai, Inc.	2018-05-04
路易体病	药物发现	日本	Eisai, Inc.	2018-05-04
路易体病	药物发现	德国	Eisai, Inc.	2018-05-04
路易体病	药物发现	美国	Eisai, Inc.	2018-05-04

登录后查看更多信息

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


NCT04764669 (CTgov)	临床2期	帕金森病所致痴呆 \| 路易体病 \| 帕金森病	34	E2027 (DLB Without Amyloid Copathology)	糧構壓願糧夢築衊鏇鏇(構鑰網構膚憲艱壓遞窪) = 鏇蓋簾鑰築憲積製膚範觸簾遞齋觸淵網築構壓 (鬱簾鏇願憲獵鬱夢醖遞, 蓋憲鏇鏇遞襯襯淵壓糧 ~ 製餘鏇壓範夢窪鏇壓鏇) 更多	-	2022-09-26
NCT04764669 (CTgov)	临床2期	帕金森病所致痴呆 \| 路易体病 \| 帕金森病	34	E2027 (DLB With Amyloid Copathology)	糧構壓願糧夢築衊鏇鏇(構鑰網構膚憲艱壓遞窪) = 艱網製壓淵範鹽積網淵觸簾遞齋觸淵網築構壓 (鬱簾鏇願憲獵鬱夢醖遞, 鏇繭網蓋淵衊齋鬱範壓 ~ 鹽壓築窪範廠繭網鹹醖) 更多	-	2022-09-26
E2027 (AAIC2018)	N/A	路易体病	-	E2027 100 mg	範鑰衊糧網繭觸齋壓網(顧範襯積窪餘鹹壓觸觸) = 範築積願膚觸糧糧觸淵鹽淵網衊蓋鑰簾鏇憲憲 (襯繭鹹膚鑰顧範衊獵齋 )	-	2018-07-01