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PDE4D：一种多用途的药理学靶点。

PDE4D: A Multipurpose Pharmacological Target.

机构信息

Department of Pharmacy (DIFAR), University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy.

出版信息

Int J Mol Sci. 2024 Jul 24;25(15):8052. doi: 10.3390/ijms25158052.

DOI:10.3390/ijms25158052
PMID:39125619
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11311937/
Abstract

Phosphodiesterase 4 (PDE4) enzymes catalyze cyclic adenosine monophosphate (cAMP) hydrolysis and are involved in a variety of physiological processes, including brain function, monocyte and macrophage activation, and neutrophil infiltration. Among different PDE4 isoforms, Phosphodiesterases 4D (PDE4Ds) play a fundamental role in cognitive, learning and memory consolidation processes and cancer development. Selective PDE4D inhibitors (PDE4Dis) could represent an innovative and valid therapeutic strategy for the treatment of various neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's, and Lou Gehrig's diseases, but also for stroke, traumatic brain and spinal cord injury, mild cognitive impairment, and all demyelinating diseases such as multiple sclerosis. In addition, small molecules able to block PDE4D isoforms have been recently studied for the treatment of specific cancer types, particularly hepatocellular carcinoma and breast cancer. This review overviews the PDE4DIsso far identified and provides useful information, from a medicinal chemistry point of view, for the development of a novel series of compounds with improved pharmacological properties.

摘要

磷酸二酯酶 4（PDE4）酶催化环腺苷单磷酸（cAMP）水解，参与多种生理过程，包括大脑功能、单核细胞和巨噬细胞激活以及中性粒细胞浸润。在不同的 PDE4 同工型中，磷酸二酯酶 4D（PDE4D）在认知、学习和记忆巩固过程以及癌症发展中起着至关重要的作用。选择性 PDE4D 抑制剂（PDE4Di）可能代表了一种创新而有效的治疗策略，可用于治疗各种神经退行性疾病，如阿尔茨海默病、帕金森病、亨廷顿病和葛雷克氏病，还可用于治疗中风、创伤性脑和脊髓损伤、轻度认知障碍以及所有脱髓鞘疾病，如多发性硬化症。此外，最近还研究了能够阻断 PDE4D 同工型的小分子，用于治疗特定类型的癌症，特别是肝癌和乳腺癌。本综述概述了迄今为止已鉴定的 PDE4Di，并从药物化学的角度提供了有用的信息，以开发具有改善的药理特性的新型化合物系列。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f144/11311937/8669dc41965f/ijms-25-08052-g012.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f144/11311937/60fc9f608648/ijms-25-08052-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f144/11311937/d2379e8cbc2d/ijms-25-08052-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f144/11311937/0b164c6419ca/ijms-25-08052-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f144/11311937/30f2416123b9/ijms-25-08052-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f144/11311937/9f4fb217332e/ijms-25-08052-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f144/11311937/8669dc41965f/ijms-25-08052-g012.jpg

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