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Phosphodiesterase 9 inhibitor

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Class of drug

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, hepatic fibrosis, Alzheimer's disease, schizophrenia, other psychotic disorders, heart failure, and sickle cell anemia. Drug candidates include CRD-733, osoresnontrine, tovinontrine, and PF-04447943. Cannabidiol acts as a PDE9 inhibitor in vitro. There are no PDE9 inhibitors that have been approved as of 2023.

References

  1. ^ Zheng, Lei; Zhou, Zhong-Zhen (November 2023). "An overview of phosphodiesterase 9 inhibitors: Insights from skeletal structure, pharmacophores, and therapeutic potential". European Journal of Medicinal Chemistry. 259: 115682. doi:10.1016/j.ejmech.2023.115682.
  2. 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. (1 November 2021). "Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice". The Journal of Clinical Investigation. 131 (21). doi:10.1172/JCI148798. ISSN 0021-9738. PMC 8553561.
  3. Wu, Yinuo; Wang, Quan; Jiang, Mei-Yan; Huang, Yi-You; Zhu, Ziran; Han, Chuan; Tian, Yi-Jing; Zhang, Bei; Luo, Hai-Bin (8 July 2021). "Discovery of Potent Phosphodiesterase-9 Inhibitors for the Treatment of Hepatic Fibrosis". Journal of Medicinal Chemistry. 64 (13): 9537–9549. doi:10.1021/acs.jmedchem.1c00862. ISSN 0022-2623.
  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. (January 2021). "CRD-733, a Novel PDE9 (Phosphodiesterase 9) Inhibitor, Reverses Pressure Overload–Induced Heart Failure". Circulation: Heart Failure. 14 (1). doi:10.1161/CIRCHEARTFAILURE.120.007300. ISSN 1941-3289. PMC 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 (2023). "Virtual screening and in vitro experiments highlight cannabidiol as a drug‐like phosphodiesterase 9 inhibitor". European Journal of Neuroscience. 57 (12): 1954–1965. doi:10.1111/ejn.15869. hdl:2158/1322316.


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