Delving into the Latest Updates on E-2027 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Irsenontrine, Irsenontrine maleate

+ [5]

Target

PDE9A

Action

inhibitors

Mechanism

PDE9A inhibitors(Phosphodiesterase 9A inhibitors)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication

Parkinson Disease

Inactive Indication

Dementia due to Parkinson's diseaseLewy Body Disease

Originator Organization

Eisai Co., Ltd.

Active Organization

Eisai Co., Ltd.

Inactive Organization

Eisai, Inc.

License Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC26H26N4O7

InChIKeyAFKSGMDXSLTKSU-DASCVMRKSA-N

CAS Registry1630083-70-3

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.

Start Date04 May 2018

Sponsor / Collaborator

Eisai, Inc.

100 Clinical Results associated with E-2027

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100 Translational Medicine associated with E-2027

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100 Patents (Medical) associated with E-2027

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6

Literatures (Medical) associated with E-2027

01 Aug 2025·Neuropharmacology

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

Article

Author: 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.

01 Jun 2025·Neural Regeneration Research

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

Article

Author: 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.

01 Oct 2023·Current Neurology and Neuroscience Reports

Lewy Body Dementia: An Overview of Promising Therapeutics

Review

Author: 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 Deals associated with E-2027

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Phase 3	-	Eisai Co., Ltd.	-
Dementia due to Parkinson's disease	Discovery	Canada	Eisai, Inc.	25 Feb 2021
Dementia due to Parkinson's disease	Discovery	United States	Eisai, Inc.	25 Feb 2021
Lewy Body Disease	Discovery	United Kingdom	Eisai, Inc.	04 May 2018
Lewy Body Disease	Discovery	France	Eisai, Inc.	04 May 2018
Lewy Body Disease	Discovery	Italy	Eisai, Inc.	04 May 2018
Lewy Body Disease	Discovery	Spain	Eisai, Inc.	04 May 2018
Lewy Body Disease	Discovery	Japan	Eisai, Inc.	04 May 2018
Lewy Body Disease	Discovery	Germany	Eisai, Inc.	04 May 2018
Lewy Body Disease	Discovery	United States	Eisai, Inc.	04 May 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04764669 (CTgov)	Phase 2	Dementia due to Parkinson's disease \| Lewy Body Disease \| Parkinson Disease	34	E2027 (DLB Without Amyloid Copathology)	lfcxxmvpyp(vggucrbxqg) = npdiwsyzmm nvsnzhqnze (ftqqsscdek, zxmrjzwyls - bcfgtvyqsm) View more	-	26 Sep 2022
NCT04764669 (CTgov)	Phase 2		34	E2027 (DLB With Amyloid Copathology)	lfcxxmvpyp(vggucrbxqg) = zxbkakdgdc nvsnzhqnze (ftqqsscdek, aryvseehen - mkpzqysszo) View more	-	26 Sep 2022
E2027 (AAIC2018)	Not Applicable	Lewy Body Disease	-	E2027 100 mg	ywckbaobmi(hbnighyrvh) = kylfsrkfdp mfqwflwisu (kzixcdirzj )	-	01 Jul 2018