Last update 19 Sep 2024

PDE12

Last update 19 Sep 2024

Basic Info

Synonyms

2-PDE, 2'-PDE, 2',5'-phosphodiesterase 12

+ [5]

Introduction

Enzyme that cleaves 2',5'-phosphodiester bond linking adenosines of the 5'-triphosphorylated oligoadenylates, triphosphorylated oligoadenylates referred as 2-5A modulates the 2-5A system. Degrades triphosphorylated 2-5A to produce AMP and ATP (PubMed:26055709). Also cleaves 3',5'-phosphodiester bond of oligoadenylates (PubMed:21666256, PubMed:30389976, PubMed:26055709). Plays a role as a negative regulator of the 2-5A system that is one of the major pathways for antiviral and antitumor functions induced by interferons (IFNs). Suppression of this enzyme increases cellular 2-5A levels and decreases viral replication in cultured small-airway epithelial cells and Hela cells (PubMed:26055709).

100 Clinical Results associated with PDE12

100 Translational Medicine associated with PDE12

0 Patents (Medical) associated with PDE12

Literatures (Medical) associated with PDE12

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.

01 Mar 2024·European Journal of Pharmacology

PDE12 disrupts mitochondrial oxidative phosphorylation and mediates mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis

Article

Author: Shi, Yuqing ; Chen, Cailian ; Xie, Jinmei ; Chen, Linlin ; Luo, Hai-Bin ; Luo, Wen ; Xie, Xi ; Wei, Qihui

Oral submucous fibrosis (OSF) is a chronic oral mucosal disease. The pathological changes of OSF include epithelial damage and subepithelial matrix fibrosis. This study aimed to reveal the epithelial injury mechanism of OSF. A histopathological method was used to analyze oral mucosal tissue from OSF patients and OSF rats. The expression of PDE12 in the oral epithelium was analyzed by immunohistochemistry. The epithelial-mesenchymal transition (EMT) and tight junction proteins in arecoline-treated HOKs were explored by western blotting. Epithelial leakage was assessed by transepithelial electrical resistance and lucifer yellow permeability. The expression of PDE12 and the mitochondrial morphology, mitochondrial permeability transition pore opening, mitochondrial membrane potential, and mitochondrial reactive oxygen species (mtROS) were evaluated in arecoline-induced HOKs. Oxidative phosphorylation (OXPHOS) complexes and ATP content were also explored in HOKs. The results showed significant overexpression of PDE12 in oral mucosal tissue from OSF patients and rats. PDE12 was also overexpressed and aggregated in mitochondria in arecoline-induced HOKs, resulting in dysfunction of OXPHOS and impaired mitochondrial function. An EMT, disruption of tight junctions with epithelial leakage, and extracellular matrix remodeling were also observed. PDE12 overexpression induced by PDE12 plasmid transfection enhanced the mtROS level and interfered with occludin protein localization in HOKs. Interestingly, knockdown of PDE12 clearly ameliorated arecoline-induced mitochondrial dysfunction and epithelial barrier dysfunction in HOKs. Therefore, we concluded that overexpression of PDE12 impaired mitochondrial OXPHOS and mitochondrial function and subsequently impaired epithelial barrier function, ultimately leading to OSF. We suggest that PDE12 may be a new potential target against OSF.

01 Jul 2023·The Journal of general virology

Inhibition of phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2.

Article

Author: Thomas, Howard ; Wand, Matthew ; Beasley, David W C ; Carroll, Miles W ; Dejnirattisai, Wanwissa ; Karayiannis, Peter ; Tree, Julia A ; Sadiq, Fouzia ; Mongkolsapaya, Juthathip ; Thursz, Mark ; Screaton, Gavin ; Matthews, Ian ; Elmore, Michael J

The 2',5'- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL activity in infected cells. We aimed to investigate PDE12 as a potential pan-RNA virus antiviral drug target and develop PDE12 inhibitors that elicit antiviral activity against a range of viruses. A library of 18 000 small molecules was screened for PDE12 inhibitor activity using a fluorescent probe specific for PDE12. The lead compounds (CO-17 or CO-63) were tested in cell-based antiviral assays using encephalomyocarditis virus (EMCV), hepatitis C virus (HCV), dengue virus (DENV), West Nile virus (WNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in vitro. Cross reactivity of PDE12 inhibitors with other PDEs and in vivo toxicity were measured. In EMCV assays, CO-17 potentiated the effect of IFNα by 3 log₁₀. The compounds were selective for PDE12 when tested against a panel of other PDEs and non-toxic at up to 42 mg kg^-1 in rats in vivo. Thus, we have identified PDE12 inhibitors (CO-17 and CO-63), and established the principle that inhibitors of PDE12 have antiviral properties. Early studies suggest these PDE12 inhibitors are well tolerated at the therapeutic range, and reduce viral load in studies of DENV, HCV, WNV and SARS-CoV-2 in human cells and WNV in a mouse model.

News (Medical) associated with PDE12

01 Nov 2022

·www.prnewswire.com

Phosphodiesterase (PDE) Inhibitors Market to Grow by USD 2.86 Bn, 40% of Market Growth to Originate from North America - Technavio

NEW YORK, Nov. 1, 2022 /PRNewswire/ -- The phosphodiesterase (PDE) inhibitors market size is expected to grow by USD 2.86 billion from 2021 to 2026. In addition, the growth momentum of the market will accelerate at a CAGR of 5.81% during the forecast period. The market has been segmented by application (oral, topical, and other ROA) and geography (North America, Europe, Asia, and Rest of World (ROW)). Find a comprehensive report summary that describes the market size and forecast along with the research methodology. The FREE sample report is available in PDF format Continue Reading Technavio has announced its latest market research report titled Global Phosphodiesterase (PDE) Inhibitors Market 2022-2026 Phosphodiesterase (PDE) Inhibitors Market: Segmentation Analysis By geography, North America will lead the thermostatic radiator valve market during the forecast period. The region will account for 40% of the market's growth. The increased consumption of alcohol, tobacco, and adoption of urban lifestyle are the major factors that are contributing to the increased patient pool with lifestyle-related diseases, and thus driving the PDE inhibitors market growth in the region during the forecast period. Get lifetime access to our Technavio Insights! Subscribe to our "Basic Plan" billed annually at USD 5000 By application, the oral segment will be the largest contributor to market growth during the forecast period. The oral segment is dominated by PDE inhibitors formulated in tablet dosage forms. Tablets are the most commonly used solid dosage forms, owing to their advantages and increasing popularity. The rising prevalence of various chronic diseases will ensure the continuous adoption of oral PDE inhibitors for their treatment, which would drive segment growth in the coming years. Learn about the contribution of each segment summarized in concise infographics and thorough descriptions. Buy Now to gain access to detailed information about each segment Phosphodiesterase (PDE) Inhibitors Market: Driver and Trend One of the key factors driving the global phosphodiesterase inhibitors industry growth is the growing adoption of poor lifestyle habits, leading to chronic diseases. As per the CDC, excessive alcohol consumption accounts for approximately 88,000 deaths every year in the US. Working adults aged between 20 and 64 years account for 1 in 10 deaths due to excessive alcohol intake. CDC also estimates that nearly 2,000 people smoke their first cigarette before the age of 18 years. Of these, more than 300 people become daily cigarette smokers. Cigarette smoking is responsible for more than 480,000 deaths every year, including 41,000 deaths due to second-hand smoke. Other factors such as rapid urbanization and modernization have further led to the adoption of poor lifestyle habits, which will further increase the risk, thereby, driving the market growth. The application of novel technologies for PDE inhibitors development is one of the key phosphodiesterase inhibitors market trends that is expected to impact the industry positively in the forecast period. PDE5 enzymes have an amino acid sequence and molecular structure similar to PDE6 and PDE11 and, hence, first-generation PDE5 inhibitors, such as sildenafil and vardenafil, are also competitive inhibitors of PDE6 and PDE11. The application of novel technologies for the development of PDE5 inhibitors is required to decrease their cross-reactivity with PDE6 and PDE11 enzymes. A similarity-based virtual screening technique, such as ZINC database, is used for this. In addition, PDE5 inhibitors, such as tadalafil, are known to block the potassium (K)-dependent HERG1 channel, the cardiac toxicity of the drug was tested through this database. The results thus obtained are of immense importance for researchers to design and develop novel, selective, and safe PDE5 inhibitors, which will further support the market growth. Identify key trends, drivers, and challenges in the market, which will help vendors improve their strategies to stay ahead of their competitors. View our FREE PDF Sample Report Related Reports: Alpha Glucosidase Inhibitors Market by Disease Type and Geography – Forecast and Analysis 2022-2026: The alpha-glucosidase inhibitors market share is expected to increase by USD 567.96 million from 2021 to 2026. Hedgehog Pathway Inhibitors Market by Indication and Geography – Forecast and Analysis 2022-2026: The hedgehog pathway inhibitors market share is expected to increase by USD 385.52 million from 2021 to 2026. Table of Contents: 1 Executive Summary 1.1 Market Overview Exhibit 01: Executive Summary – Chart on Market Overview Exhibit 02: Executive Summary – Data Table on Market Overview Exhibit 03: Executive Summary – Chart on Global Market Characteristics Exhibit 04: Executive Summary – Chart on Market by Geography Exhibit 05: Executive Summary – Chart on Market Segmentation by Application Exhibit 06: Executive Summary – Chart on Incremental Growth Exhibit 07: Executive Summary – Data Table on Incremental Growth Exhibit 08: Executive Summary – Chart on Vendor Market Positioning 2 Market Landscape 2.1 Market ecosystem Exhibit 09: Parent market Exhibit 10: Market Characteristics 3 Market Sizing 3.1 Market Definition Exhibit 11: Offerings of vendors included in the market definition 3.2 Market segment analysis Exhibit 12: Market segments 3.3 Market size 2021 3.4 Market outlook: Forecast for 2021-2026 Exhibit 13: Chart on Global - Market size and forecast 2021-2026 ($ million) Exhibit 14: Data Table on Global - Market size and forecast 2021-2026 ($ million) Exhibit 15: Chart on Global Market: Year-over-year growth 2021-2026 (%) Exhibit 16: Data Table on Global Market: Year-over-year growth 2021-2026 (%) 4 Five Forces Analysis 4.1 Five forces summary Exhibit 17: Five forces analysis - Comparison between 2021 and 2026 4.2 Bargaining power of buyers Exhibit 18: Chart on Bargaining power of buyers – Impact of key factors 2021 and 2026 4.3 Bargaining power of suppliers Exhibit 19: Bargaining power of suppliers – Impact of key factors in 2021 and 2026 4.4 Threat of new entrants Exhibit 20: Threat of new entrants – Impact of key factors in 2021 and 2026 4.5 Threat of substitutes Exhibit 21: Threat of substitutes – Impact of key factors in 2021 and 2026 4.6 Threat of rivalry Exhibit 22: Threat of rivalry – Impact of key factors in 2021 and 2026 4.7 Market condition Exhibit 23: Chart on Market condition - Five forces 2021 and 2026 5 Market Segmentation by Application 5.1 Market segments Exhibit 24: Chart on Application - Market share 2021-2026 (%) Exhibit 25: Data Table on Application - Market share 2021-2026 (%) 5.2 Comparison by Application Exhibit 26: Chart on Comparison by Application Exhibit 27: Data Table on Comparison by Application 5.3 Oral - Market size and forecast 2021-2026 Exhibit 28: Chart on Oral - Market size and forecast 2021-2026 ($ million) Exhibit 29: Data Table on Oral - Market size and forecast 2021-2026 ($ million) Exhibit 30: Chart on Oral - Year-over-year growth 2021-2026 (%) Exhibit 31: Data Table on Oral - Year-over-year growth 2021-2026 (%) 5.4 Topical - Market size and forecast 2021-2026 Exhibit 32: Chart on Topical - Market size and forecast 2021-2026 ($ million) Exhibit 33: Data Table on Topical - Market size and forecast 2021-2026 ($ million) Exhibit 34: Chart on Topical - Year-over-year growth 2021-2026 (%) Exhibit 35: Data Table on Topical - Year-over-year growth 2021-2026 (%) 5.5 Other ROA - Market size and forecast 2021-2026 Exhibit 36: Chart on Other ROA - Market size and forecast 2021-2026 ($ million) Exhibit 37: Data Table on Other ROA - Market size and forecast 2021-2026 ($ million) Exhibit 38: Chart on Other ROA - Year-over-year growth 2021-2026 (%) Exhibit 39: Data Table on Other ROA - Year-over-year growth 2021-2026 (%) 5.6 Market opportunity by Application Exhibit 40: Market opportunity by Application ($ million) 6 Customer Landscape 6.1 Customer landscape overview Exhibit 41: Analysis of price sensitivity, lifecycle, customer purchase basket, adoption rates, and purchase criteria 7 Geographic Landscape 7.1 Geographic segmentation Exhibit 42: Chart on Market share by geography 2021-2026 (%) Exhibit 43: Data Table on Market share by geography 2021-2026 (%) 7.2 Geographic comparison Exhibit 44: Chart on Geographic comparison Exhibit 45: Data Table on Geographic comparison 7.3 North America - Market size and forecast 2021-2026 Exhibit 46: Chart on North America - Market size and forecast 2021-2026 ($ million) Exhibit 47: Data Table on North America - Market size and forecast 2021-2026 ($ million) Exhibit 48: Chart on North America - Year-over-year growth 2021-2026 (%) Exhibit 49: Data Table on North America - Year-over-year growth 2021-2026 (%) 7.4 Europe - Market size and forecast 2021-2026 Exhibit 50: Chart on Europe - Market size and forecast 2021-2026 ($ million) Exhibit 51: Data Table on Europe - Market size and forecast 2021-2026 ($ million) Exhibit 52: Chart on Europe - Year-over-year growth 2021-2026 (%) Exhibit 53: Data Table on Europe - Year-over-year growth 2021-2026 (%) 7.5 Asia - Market size and forecast 2021-2026 Exhibit 54: Chart on Asia - Market size and forecast 2021-2026 ($ million) Exhibit 55: Data Table on Asia - Market size and forecast 2021-2026 ($ million) Exhibit 56: Chart on Asia - Year-over-year growth 2021-2026 (%) Exhibit 57: Data Table on Asia - Year-over-year growth 2021-2026 (%) 7.6 Rest of World (ROW) - Market size and forecast 2021-2026 Exhibit 58: Chart on Rest of World (ROW) - Market size and forecast 2021-2026 ($ million) Exhibit 59: Data Table on Rest of World (ROW) - Market size and forecast 2021-2026 ($ million) Exhibit 60: Chart on Rest of World (ROW) - Year-over-year growth 2021-2026 (%) Exhibit 61: Data Table on Rest of World (ROW) - Year-over-year growth 2021-2026 (%) 7.7 US - Market size and forecast 2021-2026 Exhibit 62: Chart on US - Market size and forecast 2021-2026 ($ million) Exhibit 63: Data Table on US - Market size and forecast 2021-2026 ($ million) Exhibit 64: Chart on US - Year-over-year growth 2021-2026 (%) Exhibit 65: Data Table on US - Year-over-year growth 2021-2026 (%) 7.8 Germany - Market size and forecast 2021-2026 Exhibit 66: Chart on Germany - Market size and forecast 2021-2026 ($ million) Exhibit 67: Data Table on Germany - Market size and forecast 2021-2026 ($ million) Exhibit 68: Chart on Germany - Year-over-year growth 2021-2026 (%) Exhibit 69: Data Table on Germany - Year-over-year growth 2021-2026 (%) 7.9 UK - Market size and forecast 2021-2026 Exhibit 70: Chart on UK - Market size and forecast 2021-2026 ($ million) Exhibit 71: Data Table on UK - Market size and forecast 2021-2026 ($ million) Exhibit 72: Chart on UK - Year-over-year growth 2021-2026 (%) Exhibit 73: Data Table on UK - Year-over-year growth 2021-2026 (%) 7.10 China - Market size and forecast 2021-2026 Exhibit 74: Chart on China - Market size and forecast 2021-2026 ($ million) Exhibit 75: Data Table on China - Market size and forecast 2021-2026 ($ million) Exhibit 76: Chart on China - Year-over-year growth 2021-2026 (%) Exhibit 77: Data Table on China - Year-over-year growth 2021-2026 (%) 7.11 Canada - Market size and forecast 2021-2026 Exhibit 78: Chart on Canada - Market size and forecast 2021-2026 ($ million) Exhibit 79: Data Table on Canada - Market size and forecast 2021-2026 ($ million) Exhibit 80: Chart on Canada - Year-over-year growth 2021-2026 (%) Exhibit 81: Data Table on Canada - Year-over-year growth 2021-2026 (%) 7.12 Market opportunity by geography Exhibit 82: Market opportunity by geography ($ million) 8 Drivers, Challenges, and Trends 8.1 Market drivers 8.2 Market challenges 8.3 Impact of drivers and challenges Exhibit 83: Impact of drivers and challenges in 2021 and 2026 8.4 Market trends 9 Vendor Landscape 9.1 Overview 9.2 Vendor landscape Exhibit 84: Overview on Criticality of inputs and Factors of differentiation 9.3 Landscape disruption Exhibit 85: Overview on factors of disruption 9.4 Industry risks Exhibit 86: Impact of key risks on business 10 Vendor Analysis 10.1 Vendors covered Exhibit 87: Vendors covered 10.2 Market positioning of vendors Exhibit 88: Matrix on vendor position and classification 10.3 Bayer AG Exhibit 89: Bayer AG - Overview Exhibit 90: Bayer AG - Business segments Exhibit 91: Bayer AG - Key offerings Exhibit 92: Bayer AG - Segment focus 10.4 Cristalia laboratory Exhibit 93: Cristalia laboratory - Overview Exhibit 94: Cristalia laboratory - Product / Service Exhibit 95: Cristalia laboratory - Key offerings 10.5 Dong A Socio Holdings Co. Ltd. Exhibit 96: Dong A Socio Holdings Co. Ltd. - Overview Exhibit 97: Dong A Socio Holdings Co. Ltd. - Product / Service Exhibit 98: Dong A Socio Holdings Co. Ltd. - Key offerings 10.6 Dr. Reddys Laboratories Ltd. Exhibit 99: Dr. Reddys Laboratories Ltd. - Overview Exhibit 100: Dr. Reddys Laboratories Ltd. - Business segments Exhibit 101: Dr. Reddys Laboratories Ltd. - Key offerings Exhibit 102: Dr. Reddys Laboratories Ltd. - Segment focus 10.7 Eli Lilly and Co. Exhibit 103: Eli Lilly and Co. - Overview Exhibit 104: Eli Lilly and Co. - Product / Service Exhibit 105: Eli Lilly and Co. - Key offerings 10.8 GlaxoSmithKline Plc Exhibit 106: GlaxoSmithKline Plc - Overview Exhibit 107: GlaxoSmithKline Plc - Business segments Exhibit 108: GlaxoSmithKline Plc - Key news Exhibit 109: GlaxoSmithKline Plc - Key offerings Exhibit 110: GlaxoSmithKline Plc - Segment focus 10.9 Pfizer Inc. Exhibit 111: Pfizer Inc. - Overview Exhibit 112: Pfizer Inc. - Product / Service Exhibit 113: Pfizer Inc. - Key news Exhibit 114: Pfizer Inc. - Key offerings 10.10 Sun Pharmaceutical Industries Ltd. Exhibit 115: Sun Pharmaceutical Industries Ltd. - Overview Exhibit 116: Sun Pharmaceutical Industries Ltd. - Product / Service Exhibit 117: Sun Pharmaceutical Industries Ltd. - Key offerings 10.11 Teva Pharmaceutical Industries Ltd. Exhibit 118: Teva Pharmaceutical Industries Ltd. - Overview Exhibit 119: Teva Pharmaceutical Industries Ltd. - Business segments Exhibit 120: Teva Pharmaceutical Industries Ltd. - Key news Exhibit 121: Teva Pharmaceutical Industries Ltd. - Key offerings Exhibit 122: Teva Pharmaceutical Industries Ltd. - Segment focus 10.12 VIVUS LLC Exhibit 123: VIVUS LLC - Overview Exhibit 124: VIVUS LLC - Product / Service Exhibit 125: VIVUS LLC - Key offerings 11 Appendix 11.1 Scope of the report 11.2 Inclusions and exclusions checklist Exhibit 126: Inclusions checklist Exhibit 127: Exclusions checklist 11.3 Currency conversion rates for US$ Exhibit 128: Currency conversion rates for US$ 11.4 Research methodology Exhibit 129: Research methodology Exhibit 130: Validation techniques employed for market sizing Exhibit 131: Information sources 11.5 List of abbreviations Exhibit 132: List of abbreviations About Technavio Technavio is a leading global technology research and advisory company. Their research and analysis focus on emerging market trends and provide actionable insights to help businesses identify market opportunities and develop effective strategies to optimize their market positions. With over 500 specialized analysts, Technavio's report library consists of more than 17,000 reports and counting, covering 800 technologies, spanning 50 countries. Their client base consists of enterprises of all sizes, including more than 100 Fortune 500 companies. This growing client base relies on Technavio's comprehensive coverage, extensive research, and actionable market insights to identify opportunities in existing and potential markets and assess their competitive positions within changing market scenarios. Contacts Technavio Research Jesse Maida Media & Marketing Executive US: +1 844 364 1100 UK: +44 203 893 3200 Email: [email protected] Website: SOURCE Technavio

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