Phosphodiesterase 9 inhibitor explained

Phosphodiesterase 9 inhibitors or PDE9 inhibitors are a class of drugs that work by inhibiting the activity of PDE9. The first compound with this effect, BAY 73-6691, was reported in 2004. PDE9 inhibitors are under investigation for the treatment of obesity,[1] hepatic fibrosis,[2] Alzheimer's disease, schizophrenia, other psychotic disorders, heart failure, and sickle cell anemia.[3] Drug candidates include CRD-733,[4] osoresnontrine, tovinontrine, and PF-04447943.[3] Cannabidiol acts as a PDE9 inhibitor in vitro.[5] There are no PDE9 inhibitors that have been approved as of 2023.[3]

Notes and References

  1. Mishra . Sumita . Sadagopan . Nandhini . Dunkerly-Eyring . Brittany . Rodriguez . Susana . Sarver . Dylan C. . Ceddia . Ryan P. . Murphy . Sean A. . Knutsdottir . Hildur . Jani . Vivek P. . Ashok . Deepthi . Oeing . Christian U. . O’Rourke . Brian . Gangoiti . Jon A. . Sears . Dorothy D. . Wong . G. William . Collins . Sheila . Kass . David A. . Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice . The Journal of Clinical Investigation . 1 November 2021 . 131 . 21 . 10.1172/JCI148798 . en . 0021-9738. free . 8553561 .
  2. Wu . Yinuo . Wang . Quan . Jiang . Mei-Yan . Huang . Yi-You . Zhu . Ziran . Han . Chuan . Tian . Yi-Jing . Zhang . Bei . Luo . Hai-Bin . Discovery of Potent Phosphodiesterase-9 Inhibitors for the Treatment of Hepatic Fibrosis . Journal of Medicinal Chemistry . 8 July 2021 . 64 . 13 . 9537–9549 . 10.1021/acs.jmedchem.1c00862 . en . 0022-2623.
  3. Zheng . Lei . Zhou . Zhong-Zhen . An overview of phosphodiesterase 9 inhibitors: Insights from skeletal structure, pharmacophores, and therapeutic potential . European Journal of Medicinal Chemistry . November 2023 . 259 . 115682 . 10.1016/j.ejmech.2023.115682.
  4. Richards . Daniel A. . Aronovitz . Mark J. . Liu . Peiwen . Martin . Gregory L. . Tam . Kelly . Pande . Suchita . Karas . Richard H. . Bloomfield . Daniel M. . Mendelsohn . Michael E. . Blanton . Robert M. . CRD-733, a Novel PDE9 (Phosphodiesterase 9) Inhibitor, Reverses Pressure Overload–Induced Heart Failure . Circulation: Heart Failure . January 2021 . 14 . 1 . 10.1161/CIRCHEARTFAILURE.120.007300 . en . 1941-3289. free . 8451972 .
  5. Ribaudo . Giovanni . Landucci . Elisa . Giannangeli . Matteo . Mazzantini . Costanza . Maccarinelli . Giuseppina . Mastinu . Andrea . Bonini . Sara Anna . Memo . Maurizio . Pellegrini‐Giampietro . Domenico E. . Gianoncelli . Alessandra . Virtual screening and in vitro experiments highlight cannabidiol as a drug‐like phosphodiesterase 9 inhibitor . European Journal of Neuroscience . 2023 . 57 . 12 . 1954–1965 . 10.1111/ejn.15869. 2158/1322316 . free .

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