Last update 01 Nov 2024

PDE2A

Last update 01 Nov 2024

Basic Info

Synonyms

cGMP-dependent 3',5'-cyclic phosphodiesterase, CGS-PDE, cGSPDE

+ [5]

Introduction

Regulates mitochondrial cAMP levels and respiration (By similarity). Involved in the regulation of mitochondria morphology/dynamics and apoptotic cell death via local modulation of cAMP/PKA signaling in the mitochondrion, including the monitoring of local cAMP levels at the outer mitochondrial membrane and of PKA-dependent phosphorylation of DNM1L (PubMed:28463107). cGMP-activated cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:9210593, PubMed:29392776, PubMed:15938621). Has a higher efficiency with cGMP compared to cAMP (PubMed:15938621). Plays a role in cell growth and migration (PubMed:24705027).

Drugs associated with PDE2A

Doxofylline

Target

A2aR x PDE x PDE2A

Mechanism

A2aR antagonists [+2]

Active Org.

Heilongjiang Fuhe Huaxing Pharmaceutical Group Co. Ltd. [+1]

Originator Org.-

Active Indication

Pulmonary Disease, Chronic Obstructive [+3]

Inactive Indication

Bronchiectasis

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date01 Oct 1988

BI-474121

Target

PDE2A

Mechanism

PDE2A inhibitors

Active Org.

C.H. Boehringer Sohn AG & Co. KG

Originator Org.

C.H. Boehringer Sohn AG & Co. KG

Active Indication-

Inactive Indication

Alzheimer Disease [+4]

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

PDE2 inhibitor(Dart NeuroScience LLC)

Target

PDE2A

Mechanism

PDE2A inhibitors

Active Org.

Dart NeuroScience LLC

Originator Org.

Dart NeuroScience LLC

Active Indication-

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with PDE2A

CTR20243683 / RecruitingNot Applicable

多索茶碱片在健康受试者中餐后状态下的单剂量、随机、开放、四周期、完全重复交叉设计的生物等效性试验

[Translation] A single-dose, randomized, open-label, four-period, completely repeated crossover bioequivalence study of doxofylline tablets in healthy volunteers in the fed state

主要研究目的：研究餐后状态下单次口服受试制剂多索茶碱片（规格：400mg，江苏宣泰药业有限公司）与参比制剂多索茶碱片（商品名：ANSIMAR®，规格：400mg，ABC FARMACEUTICI S.P.A.）在健康成年受试者体内的药代动力学，评价餐后状态下口服两种制剂的生物等效性。次要研究目的: 评价健康受试者餐后单次口服受试制剂（T）多索茶碱片和参比制剂（R）多索茶碱片（商品名：ANSIMAR®）后的安全性。

[Translation]

Main study objectives: To study the pharmacokinetics of the test preparation Doxofylline Tablets (Specification: 400mg, Jiangsu Xuantai Pharmaceutical Co., Ltd.) and the reference preparation Doxofylline Tablets (Trade name: ANSIMAR®, Specification: 400mg, ABC FARMACEUTICI S.P.A.) in healthy adult subjects after a single oral administration in the fed state, and to evaluate the bioequivalence of the two preparations after oral administration in the fed state. Secondary study objectives: To evaluate the safety of the test preparation (T) Doxofylline Tablets and the reference preparation (R) Doxofylline Tablets (Trade name: ANSIMAR®) after a single oral administration in healthy subjects.

Start Date08 Oct 2024

Sponsor / Collaborator

Jiangsu Xuantai Pharmaceutical Co., Ltd

CTRI/2024/08/071763 / Not yet recruitingNot ApplicableIIT

Comparative study of Oral Doxophylline along with Triple drug therapy versus Triple Drug Therapy in Stable Severe Chronic Obstructive Pulmonary Disease Patients A Randomised control Trial. - NIL

Start Date11 Aug 2024

Sponsor / Collaborator

SRM Hospital

CTR20242047 / CompletedNot Applicable

多索茶碱片在健康受试者中餐后状态下的单剂量、随机、开放、四周期、完全重复交叉设计的生物等效性试验

[Translation] A single-dose, randomized, open-label, four-period, completely repeated crossover bioequivalence study of doxofylline tablets in healthy volunteers in the fed state

[Translation]

Start Date29 Jun 2024

Sponsor / Collaborator

Jiangsu Xuantai Pharmaceutical Co., Ltd

100 Clinical Results associated with PDE2A

100 Translational Medicine associated with PDE2A

0 Patents (Medical) associated with PDE2A

1,127

Literatures (Medical) associated with PDE2A

01 Aug 2025·Neural Regeneration Research

Central role of altered phosphodiesterase 2-dependent signaling in the pathophysiology of cognition-based brain disorders

Article

Author: Tempio, Alessandra ; Boulksibat, Asma ; Bardoni, Barbara

01 Aug 2024·Journal of Gastrointestinal Oncology

Potential molecular metabolic mechanisms underlying the effects of cimifugin in gastric cancer through single-cell and bulk RNA sequencing combined with network pharmacology

Article

Author: Bai, Yang ; Zhang, Xinyue ; Tang, Shanneng ; Wen, Jieying ; Zhang, Yinbiao ; Zhu, Ziming ; Chen, Qiaoling ; Zhou, Xuan ; Zhang, Tao ; Li, Xiao

BackgroundGastric cancer (GC) is a leading cause of cancer-related mortality worldwide, posing a significant clinical challenge due to its complex tumor microenvironment (TME) and metabolic heterogeneity. Despite continuous improvements in treatment strategies including surgery, chemotherapy, and targeted therapies, the metabolic reprogramming in GC continues to impede treatment efficacy, highlighting an urgent need for the development of novel therapeutic strategies. This persistent issue underscores the urgent need for novel therapeutic approaches that can effectively address the diverse and dynamic characteristics of GC. Cimifugin, a traditional Chinese medicine (TCM), has garnered attention for its potential role in alleviating inflammation, neurological disorders, pain, and metabolic disorders. Its multi-targeting properties and minimal side effects suggest a broad potential for cancer management, which is currently being explored. This study aims to delineate the molecular mechanisms that cimifugin may impact within the TME and metabolic pathways of GC, with the expectation of contributing to a deeper understanding of GC and the development of innovative treatment strategies.MethodsWe identified the GC-related TME cell types and metabolic profiles and pathways by using relevant data from the single-cell RNA sequencing (scRNA-seq) database GSE134520 and the stomach adenocarcinoma (STAD) data set from The Cancer Genome Atlas (TCGA). We also assessed the effects of cimifugin on MKN28 cell proliferation, invasion, and migration. By using six public platforms, we comprehensively predicted the potential biological targets of cimifugin. Clinical prognosis and immunohistochemistry (IHC), molecular docking, and dynamics simulations were used to confirm the clinical relevance and stability of the aforementioned targets.ResultsCimifugin inhibited MKN28 cell proliferation, migration, and invasion. Cimifugin may potentially act on various metabolic pathways in GC, including folate biosynthesis, xenobiotic metabolism via cytochrome P450 (CYP), glutathione metabolism, steroid hormone biosynthesis, and tryptophan metabolism. Cimifugin was noted to stably bind to three significant core targets associated with metabolic reprogramming in GC: AKR1C2, MAOB, and PDE2A; all three targets were strongly expressed in endocrince cells, pit mucous cells (PMCs), and common myeloid progenitors (CMPs).ConclusionsWe verified the pharmacological effects of cimifugin on GC cell proliferation, invasion, and migration. AKR1C2, MAOB, and PDE2A were identified as the key targets of cimifugin in GC-related metabolic reprogramming and pathogenesis. Our research provides preliminary insights into the potential therapeutic effects of cimifugin, which could be considered for future exploration in the context of GC treatment.

01 Aug 2024·CNS & Neurological Disorders - Drug Targets

Phosphodiesterase 2 and Its Isoform A as Therapeutic Targets in the Central Nervous System Disorders

Review

Author: Lu, Jianming ; Du, Fu ; Yan, Yuqing ; Lu, Yue ; Metkar, Sanjay K. ; Xu, Ying ; Zhu, Xiongwei

Abstract:Cyclic adenosine monophosphates (cAMP) and cyclic guanosine monophosphate (cGMP) are two essential second messengers, which are hydrolyzed by phosphodiesterase's (PDEs), such as PDE-2. Pharmacological inhibition of PDE-2 (PDE2A) in the central nervous system improves cAMP and cGMP signaling, which controls downstream proteins related to neuropsychiatric, neurodegenerative, and neurodevelopmental disorders. Considering that there are no specific treatments for these disorders, PDE-2 inhibitors' development has gained more attention in the recent decade. There is high demand for developing new-generation drugs targeting PDE2 for treating diseases in the central nervous and peripheral systems. This review summarizes the relationship between PDE-2 with neuropsychiatric, neurodegenerative, and neurodevelopmental disorders as well as its possible treatment, mainly involving inhibitors of PDE2.

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PDE2A

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