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Phosphodiesterase 9 inhibitor

From Wikipedia, the free encyclopedia

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.[1] PDE9 inhibitors are under investigation for the treatment of obesity,[2] hepatic fibrosis,[3] Alzheimer's disease, schizophrenia, other psychotic disorders, heart failure, and sickle cell anemia.[1] Drug candidates include CRD-733,[4] osoresnontrine, tovinontrine, and PF-04447943.[1] Cannabidiol acts as a PDE9 inhibitor in vitro.[5] There are no PDE9 inhibitors that have been approved as of 2023.[1]

References

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  1. ^ a b c d 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.