Last update 01 Nov 2024

PDE1 x PDE5A

Last update 01 Nov 2024

Basic Info

Related Targets

PDE1PDE5A

Drugs associated with PDE1 x PDE5A

Sch-51866

Target

PDE1 x PDE5A

Mechanism

PDE1 inhibitors [+1]

Active Org.-

Originator Org.

Schering-Plough Corp.

Active Indication-

Inactive Indication

Hypertension

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Sch-59498

Target

PDE1 x PDE5A

Mechanism

PDE1 inhibitors [+1]

Active Org.-

Originator Org.

Schering-Plough Corp.

Active Indication-

Inactive Indication

Hypertension [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

BAY-383045

Target

PDE1 x PDE5A

Mechanism

PDE1 inhibitors [+1]

Active Org.-

Originator Org.

Bayer AG

Active Indication-

Inactive Indication

Angina Pectoris [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PDE1 x PDE5A

100 Translational Medicine associated with PDE1 x PDE5A

0 Patents (Medical) associated with PDE1 x PDE5A

134

Literatures (Medical) associated with PDE1 x PDE5A

01 Jun 2024·médecine/sciences

Les phosphodiestérases des nucléotides cycliques

Review

Author: Leroy, Jérôme ; Fischmeister, Rodolphe ; Kamel, Rima ; Barthou, Aurélien ; Vandecasteele, Grégoire

01 Feb 2023·Nature Reviews Cardiology

Cyclic nucleotide phosphodiesterases as therapeutic targets in cardiac hypertrophy and heart failure

Review

Author: Kamel, Rima ; Leroy, Jérôme ; Vandecasteele, Grégoire ; Fischmeister, Rodolphe

Cyclic nucleotide phosphodiesterases (PDEs) modulate the neurohormonal regulation of cardiac function by degrading cAMP and cGMP. In cardiomyocytes, multiple PDE isozymes with different enzymatic properties and subcellular localization regulate local pools of cyclic nucleotides and specific functions. This organization is heavily perturbed during cardiac hypertrophy and heart failure (HF), which can contribute to disease progression. Clinically, PDE inhibition has been considered a promising approach to compensate for the catecholamine desensitization that accompanies HF. Although PDE3 inhibitors, such as milrinone or enoximone, have been used clinically to improve systolic function and alleviate the symptoms of acute HF, their chronic use has proved to be detrimental. Other PDEs, such as PDE1, PDE2, PDE4, PDE5, PDE9 and PDE10, have emerged as new potential targets to treat HF, each having a unique role in local cyclic nucleotide signalling pathways. In this Review, we describe cAMP and cGMP signalling in cardiomyocytes and present the various PDE families expressed in the heart as well as their modifications in pathological cardiac hypertrophy and HF. We also appraise the evidence from preclinical models as well as clinical data pointing to the use of inhibitors or activators of specific PDEs that could have therapeutic potential in HF.

01 May 2022·British Journal of PharmacologyQ2 · MEDICINE

Nicotinic‐acid derivative BGP‐15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy

Q2 · MEDICINE

Article

Author: Posa, Aniko ; Raduly, Arnold ; Szilvassy, Zoltan ; Papp, Zoltan ; Lampe, Nora ; Priksz, Daniel ; Szilvassy, Judit ; Hamdani, Nazha ; Toth, Attila ; Wilisicz, Tician ; Juhasz, Bela ; Gesztelyi, Rudolf ; Kovacs, Arpad ; Kiss, Rita ; Varga, Balazs ; Sieme, Marcel ; Herwig, Melissa ; Szekeres, Reka ; Bombicz, Mariann

Background and PurposeThe small molecule BGP‐15 has been reported to alleviate symptoms of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP‐15 in a rabbit model of atherosclerotic cardiomyopathy.Experimental ApproachRabbits were maintained on standard chow (control) or atherogenic diet (hypercholesterolemic) for 16 weeks. BGP‐15 was administered intravenously (once) or orally (for 16 weeks), to assess acute and chronic effects. Cardiac function was evaluated by echocardiography, endothelium‐dependent vasorelaxation was assessed and key molecules in the protein kinase G (PKG) pathway were examined by enzyme‐linked immunosorbent assay (ELISA) and western blot. Passive force generation was investigated in skinned cardiomyocytes.Key ResultsBoth acute and chronic BGP‐15 treatments improved the diastolic performance of the diseased heart. However, vasorelaxation and serum lipid markers were unaffected. Myocardial cyclic guanosine monophosphate (cGMP) levels were elevated in the BGP‐15‐treated group, along with preserved PKG activity and increased phospholamban Ser16‐phosphorylation. PDE5 expression decreased in the BGP‐15‐treated group and PDE1 was inhibited. Cardiomyocyte passive tension reduced in BGP‐15‐treated rabbits, the ratio of titin N2BA/N2B isoforms increased and PKG‐dependent N2B‐titin phosphorylation elevated.Conclusions and ImplicationsBGP‐15 treatment improves diastolic function, reduces cardiomyocyte stiffness and restores titin compliance in a rabbit model of atherosclerotic cardiomyopathy by increasing the activity of the cGMP‐PKG pathway. As BGP‐15 has been proven to be safe, it may be clinically useful in the treatment of diastolic dysfunction.

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