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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
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3',5'-Cyclic nucleotide phosphodiesterases (PDEs, 3',5'-cyclic-nucleotide 5'-nucleotidohydrolase), E.C. 3.1.4.17, catalyse the hydrolysis of a 3',5'-cyclic nucleotide (usually cyclic AMP or cyclic GMP). Isobutylmethylxanthine is a nonselective inhibitor with an IC50 value in the millimolar range for all isoforms except PDE 8A, 8B and 9A. A 2',3'-cyclic nucleotide 3'-phosphodiesterase (E.C. 3.1.4.37 CNPase) activity is associated with myelin formation in the development of the CNS.
PDE1A (phosphodiesterase 1A) C Show summary »« Hide summary
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PDE1B (phosphodiesterase 1B) C Show summary »« Hide summary
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PDE1C (phosphodiesterase 1C) C Show summary »« Hide summary
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PDE2A (phosphodiesterase 2A) C Show summary »« Hide summary
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PDE3A (phosphodiesterase 3A)
C
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PDE3B (phosphodiesterase 3B) C Show summary »« Hide summary
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PDE4A (phosphodiesterase 4A)
C
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PDE4B (phosphodiesterase 4B)
C
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PDE4C (phosphodiesterase 4C)
C
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PDE4D (phosphodiesterase 4D)
C
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PDE5A (phosphodiesterase 5A)
C
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PDE6A (phosphodiesterase 6A) C Show summary »« Hide summary
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PDE6B (phosphodiesterase 6B)
C
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PDE6C (phosphodiesterase 6C) C Show summary »« Hide summary
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PDE6D (phosphodiesterase 6D) C Show summary »« Hide summary
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PDE6G (phosphodiesterase 6G) C Show summary »« Hide summary
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PDE6H (phosphodiesterase 6H) C Show summary »« Hide summary
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PDE7A (phosphodiesterase 7A) C Show summary »« Hide summary
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PDE7B (phosphodiesterase 7B)
C
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PDE8A (phosphodiesterase 8A)
C
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PDE8B (phosphodiesterase 8B) C Show summary »« Hide summary
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PDE9A (phosphodiesterase 9A) C Show summary »« Hide summary
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PDE10A (phosphodiesterase 10A)
C
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PDE11A (phosphodiesterase 11A) C Show summary »« Hide summary
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* Key recommended reading is highlighted with an asterisk
Das A, Durrant D, Salloum FN, Xi L, Kukreja RC. (2015) PDE5 inhibitors as therapeutics for heart disease, diabetes and cancer. Pharmacol. Ther., 147: 12-21. [PMID:25444755]
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* Klussmann E. (2016) Protein-protein interactions of PDE4 family members - Functions, interactions and therapeutic value. Cell. Signal., 28 (7): 713-8. [PMID:26498857]
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* Ntontsi P, Detta A, Bakakos P, Loukides S, Hillas G. (2019) Experimental and investigational phosphodiesterase inhibitors in development for asthma. Expert Opin Investig Drugs, 28 (3): 261-266. [PMID:30678501]
* Pauls MM, Moynihan B, Barrick TR, Kruuse C, Madigan JB, Hainsworth AH, Isaacs JD. (2018) The effect of phosphodiesterase-5 inhibitors on cerebral blood flow in humans: A systematic review. J. Cereb. Blood Flow Metab., 38 (2): 189-203. [PMID:29256324]
* Peng T, Gong J, Jin Y, Zhou Y, Tong R, Wei X, Bai L, Shi J. (2018) Inhibitors of phosphodiesterase as cancer therapeutics. Eur J Med Chem, 150: 742-756. [PMID:29574203]
Ricciarelli R, Fedele E. (2015) Phosphodiesterase 4D: an enzyme to remember. Br. J. Pharmacol., 172 (20): 4785-9. [PMID:26211680]
* Svensson F, Bender A, Bailey D. (2018) Fragment-Based Drug Discovery of Phosphodiesterase Inhibitors. J. Med. Chem., 61 (4): 1415-1424. [PMID:28800229]
* Wahlang B, McClain C, Barve S, Gobejishvili L. (2018) Role of cAMP and phosphodiesterase signaling in liver health and disease. Cell. Signal., 49: 105-115. [PMID:29902522]
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* Zagorska A, Partyka A, Bucki A, Gawalskax A, Czopek A, Pawlowski M. (2018) Phosphodiesterase 10 Inhibitors - Novel Perspectives for Psychiatric and Neurodegenerative Drug Discovery. Curr. Med. Chem., 25 (29): 3455-3481. [PMID:29521210]
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Chen Yan, Ph.D. |
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Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Enzymes. Br J Pharmacol. 176 Issue S1: S297-S396.
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PDE1A, 1B and 1C appear to act as soluble homodimers, while PDE2A is a membrane-bound homodimer. PDE3A and PDE3B are membrane-bound.
PDE4 isoforms are essentially cyclic AMP specific. The potency of YM976 at other members of the PDE4 family has not been reported. PDE4B–D long forms are inhibited by extracellular signal-regulated kinase (ERK)-mediated phosphorylation [17-18]. PDE4A–D splice variants can be membrane-bound or cytosolic [19]. PDE4 isoforms may be labelled with [3H]rolipram.
PDE6 is a membrane-bound tetramer composed of two catalytic chains (PDE6A or PDE6C and PDE6B), an inhibitory chain (PDE6G or PDE6H) and the PDE6D chain. The enzyme is essentially cyclic GMP specific and is activated by the α-subunit of transducin (Gαt) and inhibited by sildenafil, zaprinast and dipyridamole with potencies lower than those observed for PDE5A. Defects in PDE6B are a cause of retinitis pigmentosa and congenital stationary night blindness.