Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.

IF 11.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI:10.1146/annurev-pharmtox-031524-025239
Evan D Kelly, Mark J Ranek, Manling Zhang, David A Kass, Grace K Muller
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Abstract

Phosphodiesterases (PDEs) are a superfamily of enzymes that hydrolyze cyclic nucleotides. While the 11 PDE subfamilies share common features, key differences confer signaling specificity. The differences include substrate selectivity, enzymatic activity regulation, tissue expression, and subcellular localization. Selective inhibitors of each subfamily have elucidated the protean role of PDEs in normal cell function. PDEs are also linked to diseases, some of which affect the immune, cardiac, and vascular systems. Selective PDE inhibitors are clinically used to treat these specific disorders. Ongoing preclinical studies and clinical trials are likely to lead to the approval of additional PDE-targeting drugs for therapy in human disease. In this review, we discuss the structure and function of PDEs and examine current and evolving therapeutic uses of PDE inhibitors, highlighting their mechanisms and innovative applications that could further leverage this crucial family of enzymes in clinical settings.

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磷酸二酯酶:不断演变的概念和对人类治疗的影响。
磷酸二酯酶(PDE)是水解环状核苷酸的酶超家族。虽然 11 个磷酸二酯酶亚家族具有共同特征,但关键的差异赋予了信号特异性。这些差异包括底物选择性、酶活性调节、组织表达和亚细胞定位。每个亚家族的选择性抑制剂都阐明了 PDEs 对正常细胞功能的蛋白作用。PDE 还与疾病有关,其中一些疾病会影响免疫、心脏和血管系统。临床上使用选择性 PDE 抑制剂来治疗这些特定疾病。目前正在进行的临床前研究和临床试验可能会促使更多的 PDE 靶向药物获得批准,用于治疗人类疾病。在这篇综述中,我们将讨论 PDE 的结构和功能,研究 PDE 抑制剂当前和不断发展的治疗用途,重点介绍其机制和创新应用,以便在临床中进一步利用这一重要的酶家族。
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来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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