phosphodiesterase 3A

Target id: 1298

Nomenclature: phosphodiesterase 3A

Abbreviated Name: PDE3A

Family: Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs)

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for phosphodiesterase 3A in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1141 12p12.2 PDE3A phosphodiesterase 3A
Mouse - 1141 6 71.87cM Pde3a phosphodiesterase 3A, cGMP inhibited
Rat - 1141 4q44 Pde3a phosphodiesterase 3A
Previous and Unofficial Names
CGI-PDE A | phosphodiesterase 3A cGMP inhibited | phosphodiesterase 3A, cGMP-inhibited | phosphodiesterase 3A, cGMP inhibited
Database Links
BRENDA
CATH/Gene3D
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.1.4.17

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
anagrelide Hs Inhibition 7.1 – 7.3 pIC50 3-5
pIC50 7.1 – 7.3 (IC50 8.2x10-8 – 5.4x10-8 M) [3-5]
cilostazol Hs Inhibition 6.7 pIC50 7
pIC50 6.7 (IC50 2x10-7 M) [7]
milrinone Hs Inhibition 6.3 – 6.4 pIC50 2,7
pIC50 6.3 – 6.4 (IC50 4.5x10-7 – 4.4x10-7 M) [2,7]
enoximone Hs Inhibition 5.4 pIC50 8
pIC50 5.4 (IC50 3.8x10-6 M) [8]
Description: Measuring inhibition of human platelet PDE
inamrinone Hs Inhibition 4.8 pIC50 6
pIC50 4.8 (IC50 1.6x10-5 M) [6]
Description: Inhibition of PDE3 purified from human platelets, and therefore assumed to be the PDE3A subtype.
ibudilast Hs Inhibition 3.5 pIC50 1
pIC50 3.5 (IC50 2.99x10-4 M) [1]
Inhibitor Comments
Anagrelide is an approved drug inhibitor of PDE3A in platelets.
Amrinone (inamrinone) and cilostazol are significantly selective for the PDE3 isozymes over the other PDEs tested [7].

References

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1. Allcock RW, Blakli H, Jiang Z, Johnston KA, Morgan KM, Rosair GM, Iwase K, Kohno Y, Adams DR. (2011) Phosphodiesterase inhibitors. Part 1: Synthesis and structure-activity relationships of pyrazolopyridine-pyridazinone PDE inhibitors developed from ibudilast. Bioorg. Med. Chem. Lett.21 (11): 3307-12. [PMID:21530250]

2. Edmondson SD, Mastracchio A, He J, Chung CC, Forrest MJ, Hofsess S, MacIntyre E, Metzger J, O'Connor N, Patel K et al.. (2003) Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors. Bioorg. Med. Chem. Lett.13 (22): 3983-7. [PMID:14592490]

3. Jones GH, Venuti MC, Alvarez R, Bruno JJ, Berks AH, Prince A. (1987) Inhibitors of cyclic AMP phosphodiesterase. 1. Analogues of cilostamide and anagrelide. J. Med. Chem.30 (2): 295-303. [PMID:3027338]

4. Martinez GR, Walker KA, Hirschfeld DR, Bruno JJ, Yang DS, Maloney PJ. (1992) 3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase. J. Med. Chem.35 (4): 620-8. [PMID:1311763]

5. Meanwell NA, Pearce BC, Roth HR, Smith EC, Wedding DL, Wright JJ, Buchanan JO, Baryla UM, Gamberdella M, Gillespie E et al.. (1992) Inhibitors of blood platelet cAMP phosphodiesterase. 2. Structure-activity relationships associated with 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones substituted with functionalized side chains. J. Med. Chem.35 (14): 2672-87. [PMID:1321910]

6. Sircar I, Steffen RP, Bobowski G, Burke SE, Newton RS, Weishaar RE, Bristol JA, Evans DB. (1989) Cardiotonic agents. 9. Synthesis and biological evaluation of a series of (E)-4,5-dihydro-6-[2-[4-(1H-imidazol-1-yl)phenyl]ethenyl]-3 (2H)-pyridazinones: a novel class of compounds with positive inotropic, antithrombotic, and vasodilatory activities for the treatment of congestive heart failure. J. Med. Chem.32 (2): 342-50. [PMID:2536438]

7. Sudo T, Tachibana K, Toga K, Tochizawa S, Inoue Y, Kimura Y, Hidaka H. (2000) Potent effects of novel anti-platelet aggregatory cilostamide analogues on recombinant cyclic nucleotide phosphodiesterase isozyme activity. Biochem. Pharmacol.59 (4): 347-56. [PMID:10644042]

8. Venuti MC, Jones GH, Alvarez R, Bruno JJ. (1987) Inhibitors of cyclic AMP phosphodiesterase. 2. Structural variations of N-cyclohexyl-N-methyl-4-[(1,2,3,5-tetrahydro- 2-oxoimidazo[2,1-b]quinazolin-7-yl)-oxy]butyramide (RS-82856). J. Med. Chem.30 (2): 303-18. [PMID:3027339]

How to cite this page

Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs): phosphodiesterase 3A. Last modified on 10/06/2016. Accessed on 22/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1298.