The therapeutic potential of phosphodiesterase 9 (PDE9) inhibitors: a patent review (2018-present)

Expert Opin Ther Pat. 2024 Sep;34(9):759-772. doi: 10.1080/13543776.2024.2376632. Epub 2024 Jul 9.

Abstract

Introduction: Phosphodiesterase 9 (PDE9) has been demonstrated as a potential target for neurological disorders and cardiovascular diseases, such as Alzheimer's disease and heart failure. For the last few years, a series of PDE9 inhibitors with structural diversities have been developed and patented by researchers and pharmaceutical companies, providing insights into first-in-class therapies of PDE9 drug candidates.

Area covered: This review provides an overview of PDE9 inhibitors in patents from 2018 to the present.

Expert opinion: Only a few of the current PDE9 inhibitors are highly selective over other PDEs, which limits their application in pharmacological and clinical research. The design and development of highly selective PDE9 inhibitors remain the top priority in future research. The advantages of targeting PDE9 rather than other PDEs in treating neurodegenerative diseases need to be explained thoroughly. Besides, application of PDE9 inhibitor-based combination therapies sheds light on treating diabetes and refractory heart diseases. Finally, PDE9 inhibitors should be further explored in clinical indications beyond neurological disorders and cardiovascular diseases.

Keywords: Alzheimer’s disease; PDE9; Phosphodiesterase; heart failure; therapeutic targets.

Publication types

  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism
  • Animals
  • Cardiovascular Diseases* / drug therapy
  • Drug Design
  • Drug Development*
  • Humans
  • Nervous System Diseases / drug therapy
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / physiopathology
  • Patents as Topic*
  • Phosphodiesterase Inhibitors* / pharmacology

Substances

  • Phosphodiesterase Inhibitors
  • PDE9A protein, human
  • 3',5'-Cyclic-AMP Phosphodiesterases