Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery.

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) control the intracellular concentrations of cAMP and cGMP in virtually all mammalian cells. Accordingly, the PDE family regulates a myriad of physiological functions, including cell proliferation, differentiation and apoptosis, gene expression, central nervous system function, and muscle contraction. Along this line, dysfunction of PDEs has been implicated in neurodegenerative disorders, coronary artery diseases, chronic obstructive pulmonary disease, and cancer development. To date, 11 PDE families have been identified; however, their distinct roles in the various pathologies are largely unexplored and subject to contemporary research efforts. Indeed, there is growing interest for the development of isoform-selective PDE inhibitors as potential therapeutic agents. Similarly, the evolving knowledge on the various PDE isoforms has channeled the identification of new PET probes, allowing isoform-selective imaging. This review highlights recent advances in PDE-targeted PET tracer development, thereby focusing on efforts to assess disease-related PDE pathophysiology and to support isoform-selective drug discovery.

• Authors: Jiyun Sun, Zhiwei Xiao, Ahmed Haider, Catherine Gebhard, Hao Xu, Hai-Bin Luo, Han-Ting Zhang, Lee Josephson, Lu Wang, Steven H Liang
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 64 Issue 11 Pg. 7083-7109 (06 10 2021) ISSN: 1520-4804 [Electronic] United States
• PMID: 34042442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Phosphodiesterase Inhibitors
• Protein Isoforms
• Radiopharmaceuticals
• 3',5'-Cyclic-AMP Phosphodiesterases

Topics

• 3',5'-Cyclic-AMP Phosphodiesterases (antagonists & inhibitors, metabolism)
• Animals
• Drug Discovery
• Humans
• Neoplasms (diagnostic imaging, drug therapy)
• Phosphodiesterase Inhibitors (chemistry, metabolism, therapeutic use)
• Positron-Emission Tomography
• Protein Isoforms (antagonists & inhibitors, metabolism)
• Radiopharmaceuticals (chemistry, metabolism)
• Signal Transduction (drug effects)