Delving into the Latest Updates on Edelinontrine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [2]

Target

PDE9A

Action

inhibitors

Mechanism

PDE9A inhibitors(Phosphodiesterase 9A inhibitors)

Therapeutic Areas

Other Diseases

Active Indication

Cognition Disorders

Inactive Indication

Alzheimer Disease

Originator Organization

Pfizer Inc.

Active Organization

Pfizer Inc.

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC20H25N7O2

InChIKeyIWXUVYOOUMLUTQ-CZUORRHYSA-N

CAS Registry1082744-20-4

This study is being conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an investigational drug, PF-04447943, in subjects with stable sickle cell disease with and without co-administration with hydroxyurea. This study will also aid in selecting the doses for future studies and evaluation of substances in the blood which may help access the effectiveness of the drug.

Start Date01 Dec 2014

Sponsor / Collaborator

Pfizer Inc.

EUCTR2010-020427-43-DE

/ Not yet recruitingPhase 2

A PHASE 2 MULTICENTER, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP STUDY OF PF 04447943 IN SUBJECTS WITH MILD TO MODERATE ALZHEIMER’S DISEASE ON STABLE DONEPEZIL THERAPY

Start Date13 Oct 2010

Sponsor / Collaborator-

100 Clinical Results associated with Edelinontrine

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100 Translational Medicine associated with Edelinontrine

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100 Patents (Medical) associated with Edelinontrine

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40

Literatures (Medical) associated with Edelinontrine

01 Nov 2024·Microcirculation

PDE9A Inhibition Improves Coronary Microvascular Rarefaction and Left Ventricular Diastolic Dysfunction in the ZSF1 Rat Model of HFpEF

Article

Author: Lang, Liwei ; Buncha, Vadym ; Bagi, Zsolt ; Fopiano, Katie Anne ; Pearson, William M. ; Zhazykbayeva, Saltanat ; El‐Battrawy, Ibrahim ; Hamdani, Nazha ; Hardell, Davis J.

ABSTRACTObjectiveHeart failure with preserved ejection fraction (HFpEF) commonly arises from comorbid diseases, such as hypertension, obesity, and diabetes mellitus. Selective inhibition of phosphodiesterase 9A (PDE9A) has emerged as a potential therapeutic approach for treating cardiometabolic diseases. Coronary microvascular disease (CMD) is one of the key mechanisms contributing to the development of left ventricular (LV) diastolic dysfunction in HFpEF. Our study aimed to investigate the mechanisms by which PDE9A inhibition could ameliorate CMD and improve LV diastolic function in HFpEF.Methods and ResultsThe obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model of HFpEF was employed in which it was found that a progressively developing coronary microvascular rarefaction is associated with LV diastolic dysfunction when compared to lean, nondiabetic hypertensive controls. Obese ZSF1 rats had an increased cardiac expression of PDE9A. Treatment of obese ZSF1 rats with the selective PDE9A inhibitor, PF04447943 (3 mg/kg/day, oral gavage for 2 weeks), improved coronary microvascular rarefaction and LV diastolic dysfunction, which was accompanied by reduced levels of oxidative and nitrosative stress markers, hydrogen peroxide, and 3‐nitrotyrosine. Liquid chromatography–mass spectrometry (LC–MS) proteomic analysis identified peroxiredoxins (PRDX) as downregulated antioxidants in the heart of obese ZSF1 rats, whereas Western immunoblots showed that the protein level of PRDX5 was significantly increased by the PF04447943 treatment.ConclusionsThus, in the ZSF1 rat model of human HFpEF, PDE9A inhibition improves coronary vascular rarefaction and LV diastolic dysfunction, demonstrating the usefulness of PDE9A inhibitors in ameliorating CMD and LV diastolic dysfunction through augmenting PRDX‐dependent antioxidant mechanisms.

02 Jun 2024·Expert Opinion on Investigational Drugs

The role of phosphodiesterase 9A inhibitors in heart failure

Review

Author: Lanier, Gregg M ; Foroshani, Saam ; Aronow, Wilbert S ; Karp, Avrohom

INTRODUCTIONThere are currently limited effective treatments available to improve lusitropy in patients suffering from heart failure with preserved ejection fraction. The role of PDE9A in diastolic dysfunction has been well-studied over recent years, with a special focus on its association with myocardial hypertrophy. Recent insights into PDE9A inhibition have brought to light the potential for reversal of cardiac remodeling, with multiple studies showing promising results in preclinical data.AREAS COVEREDThis expert opinion provides an overview of the role of PDE9A in diastolic heart dysfunction along with the efficacy of PDE9A inhibitors in laboratory models of heart failure with preserved ejection fraction.EXPERT OPINIONThe available data on PDE9A inhibition in preclinical studies suggest that there is potential for reversal of diastolic dysfunction and myocardial hypertrophy, however, conflicting data suggests that further studies are required before progressing to clinical trials.

01 Jun 2023·European Journal of Neuroscience

Virtual screening and in vitro experiments highlight cannabidiol as a drug‐like phosphodiesterase 9 inhibitor

Article

Author: Bonini, Sara Anna ; Mastinu, Andrea ; Memo, Maurizio ; Gianoncelli, Alessandra ; Pellegrini‐Giampietro, Domenico E. ; Maccarinelli, Giuseppina ; Mazzantini, Costanza ; Landucci, Elisa ; Ribaudo, Giovanni ; Giannangeli, Matteo

AbstractThe growing interest on the therapeutic potential against neurodegeneration of Cannabis sativa extracts, and of phytocannabinoids in particular, is paralleled by a limited understanding of the undergoing biochemical pathways in which these natural compounds may be involved. Computational tools are nowadays commonly enrolled in the drug discovery workflow and can guide the investigation of macromolecular targets for such molecules. In this contribution, in silico techniques have been applied to the study of C. sativa constituents at various extents, and a total of seven phytocannabinoids and four terpenes were considered. On the side of ligand‐based virtual screening, physico‐chemical descriptors were computed and evaluated, highlighting the phytocannabinoids possessing suitable drug‐like properties to potentially target the central nervous system. Our previous findings and literature data prompted us to investigate the interaction of these molecules with phosphodiesterases (PDEs), a family of enzymes being studied for the development of therapeutic agents against neurodegeneration. Among the compounds, structure‐based techniques such as docking and molecular dynamics (MD), highlighted cannabidiol (CBD) as a potential and selective PDE9 ligand, since a promising calculated binding energy value (−9.1 kcal/mol) and a stable interaction in the MD simulation timeframe were predicted.Additionally, PDE9 inhibition assay confirmed the computational results, and showed that CBD inhibits the enzyme in the nanomolar range in vitro, paving the way for further development of this phytocannabinoid as a therapeutic option against neurodegeneration.

100 Deals associated with Edelinontrine

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11953

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cognition Disorders	Preclinical	United States	Pfizer Inc.	25 Jul 2012
Alzheimer Disease	Preclinical	Czechia	Pfizer Inc.	10 Sep 2009
Alzheimer Disease	Preclinical	Canada	Pfizer Inc.	10 Sep 2009
Alzheimer Disease	Preclinical	United States	Pfizer Inc.	10 Sep 2009
Alzheimer Disease	Preclinical	Chile	Pfizer Inc.	10 Sep 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00930059 (CTgov)	Phase 2	Alzheimer Disease	191	Placebo (Placebo)	gtfurkjnke(mrptlmdtll) = htlvyydwad zjzpiukllj (eskvfevalu, fkghdqxcnj - mbuhqhwodg) View more	-	19 Nov 2020
				PF-04447943 (PF-04447943)	gtfurkjnke(mrptlmdtll) = fhpurheqvz zjzpiukllj (eskvfevalu, uoypyivuzo - izaynzrcwe) View more
NCT00988598 (CTgov)	Phase 1	Alzheimer Disease	15	Donepezil+PF-04447943 (PF-04447943 25 mg + Donepezil)	zwamzsxkvr(zfnfzxkhyd) = eeexcvxkaf dwzoqqsrka (rmhhygtprg, aoqgiewbfn - mylqpilukn) View more	-	19 Nov 2020
				Placebo+Donepezil (Placebo + Donepezil)	zwamzsxkvr(zfnfzxkhyd) = nlkvlkwccu dwzoqqsrka (rmhhygtprg, uxrmeebrec - xsvroybgkw) View more
NCT02785770 (CTgov)	Phase 1	-	44	Placebo	omvcdjhsoj(hyrcwdsuzt) = qffgjowkiq arplwynfrf (umaepbcayp, qkeaxvpefr - lrtwcocvqp) View more	-	28 Dec 2018
NCT02114203 (CTgov)	Phase 1	Anemia, Sickle Cell	30	PF-04447943 (PF-04447943 5 mg BID)	uzgikbxkno(koaabdzzrq) = zfdbprrxjy rotujkqdgq (nhhqlledkr, ekuknieztj - ttybmrpijo) View more	-	14 Dec 2017
				PF-04447943 (PF-04447943 25 mg BID)	uzgikbxkno(koaabdzzrq) = owhxcfeqht rotujkqdgq (nhhqlledkr, rnldjeiqdd - rvzzoeehpg) View more
AAIC2010	Not Applicable	-	-	PF-04447943	(axkyguncuj) = tbcrhnguac zokincibrw (qpikfbbvhb ) View more	-	01 Jul 2010