Last update 01 Nov 2024

PDE11A

Last update 01 Nov 2024

Basic Info

Synonyms

cAMP and cGMP phosphodiesterase 11A, Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A, PDE11A

+ [1]

Introduction

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP (PubMed:10725373, PubMed:10906126, PubMed:11050148, PubMed:16330539). Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively (PubMed:10725373, PubMed:10906126, PubMed:11050148).

Drugs associated with PDE11A

PDE11A inhibitors(University of Maryland School of Medicine)

Target

PDE11A

Mechanism

PDE11A inhibitors

Active Org.

University of Maryland School of Medicine

Originator Org.

University of Maryland School of Medicine

Active Indication

Memory Disorders

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

BAY-65-6207

Target

PDE11A

Mechanism

PDE11A inhibitors

Active Org.-

Originator Org.

Bayer AG

Active Indication-

Inactive Indication

Diabetes Mellitus, Type 2

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PDE11A

100 Translational Medicine associated with PDE11A

0 Patents (Medical) associated with PDE11A

166

Literatures (Medical) associated with PDE11A

30 Sep 2024·European Journal of Endocrinology

Correction to: Analysis of genetic variants of phosphodiesterase 11A in acromegalic patients

01 Jul 2024·European Journal of Cancer

Germline NGS targeted analysis in adult patients with sporadic adrenocortical carcinoma

Article

Author: Palermo, Flavia ; Grosso, Enrico ; Scatolini, Maria ; Rossini, Elisa ; Cosentini, Deborah ; Berruti, Alfredo ; Basile, Vittoria ; Puglisi, Soraya ; Grisanti, Salvatore ; Laganà, Marta ; Saba, Laura ; Perotti, Paola ; Sigala, Sandra ; Volante, Marco ; Tomaiuolo, Pasquale ; Terzolo, Massimo

BACKGROUNDAdrenocortical carcinoma (ACC) is a rare cancer that arises sporadically or due to hereditary syndromes. Data on germline variants (GVs) in sporadic ACC are limited. Our aim was to characterize GVs of genes potentially related to adrenal diseases in 150 adult patients with sporadic ACC.METHODSThis was a retrospective analysis of stage I-IV ACC patients with sporadic ACC from two reference centers for ACC in Italy. Patients were included in the analysis if they had confirmed diagnosis of ACC, a frozen peripheral blood sample and complete clinical and follow-up data. Next generation sequencing technology was used to analyze the prevalence of GVs in a custom panel of 17 genes belonging to either cancer-predisposition genes or adrenocortical-differentiation genes categories.RESULTSWe identified 18 GVs based on their frequency, enrichment and predicted functional characteristics. We found six pathogenic (P) or likely pathogenic (LP) variants in ARMC5, CTNNB1, MSH2, PDE11A and TP53 genes; and twelve variants lacking evidence of pathogenicity. New unique P/LP variants were identified in TP53 (p.G105D) and, for the first time, in ARMC5 (p.P731R). The presence of P/LP GVs was associated with reduced survival outcomes and had a significant and independent impact on both progression-free survival and overall survival.CONCLUSIONSGVs were present in 6.7 % of patients with sporadic ACC, and we identified novel variants of ARMC5 and TP53. These findings may improve understanding of ACC pathogenesis and enable genetic counseling of patients and their families.

09 Nov 2023·Journal of Medicinal ChemistryQ1 · MEDICINE

First Optimization of Novel, Potent, Selective PDE11A4 Inhibitors for Age-Related Cognitive Decline

Q1 · MEDICINE

Article

Author: Colussi, Dennis ; Gordon, John ; Ly, Judy ; Tummalapalli, Sreedhar ; Eberhard, Jeremy ; Childers, Wayne ; Kelly, Michy P ; Lozano Gonzalez, Mariana ; Hoffman, Charles S ; Rotella, David P ; Mahmood, Shams Ul

Phosphodiesterase 11A4 (PDE11A4) is a dual-acting cyclic nucleotide hydrolase expressed in neurons in the CA1, subiculum, amygdalostriatal transition area and amygdalohippocampal area of the extended hippocampal formation. PDE11A4 is the only PDE enzyme to emanate solely from hippocampal formation, a key brain region for the formation of long-term memory. PDE11A4 expression increases in the hippocampal formation of both humans and rodents as they age. Interestingly, PDE11A knockout mice do not show age-related deficits in associative memory and show no gross histopathology. This suggests that inhibition of PDE11A4 might serve as a therapeutic option for age-related cognitive decline. A novel, yeast-based high throughput screen previously identified moderately potent, selective PDE11A4 inhibitors, and this work describes initial efforts that improved potency more than 10-fold and improved some pharmaceutical properties of one of these scaffolds, leading to selective, cell-penetrant PDE11A4 inhibitors, one of which is 10-fold more potent compared to tadalafil in cell-based activity.

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