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phosphodiesterase 3A

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Target id: 1298

Nomenclature: phosphodiesterase 3A

Abbreviated Name: PDE3A

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

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1141 12p12.2 PDE3A phosphodiesterase 3A
Mouse 6 1141 6 G2 Pde3a phosphodiesterase 3A, cGMP inhibited
Rat 6 1141 4q44 Pde3a phosphodiesterase 3A
Previous and Unofficial Names Click here for help
CGI-PDE A | phosphodiesterase 3A cGMP inhibited | phosphodiesterase 3A, cGMP-inhibited | phosphodiesterase 3A, cGMP inhibited
Database Links Click here for help
Alphafold Q14432 (Hs), Q9Z0X4 (Mm), Q62865 (Rn)
BRENDA 3.1.4.17
CATH/Gene3D 1.10.1300.10
ChEMBL Target CHEMBL241 (Hs)
DrugBank Target Q14432 (Hs)
Ensembl Gene ENSG00000172572 (Hs), ENSMUSG00000041741 (Mm), ENSRNOG00000025042 (Rn)
Entrez Gene 5139 (Hs), 54611 (Mm), 50678 (Rn)
Human Protein Atlas ENSG00000172572 (Hs)
KEGG Enzyme 3.1.4.17
KEGG Gene hsa:5139 (Hs), mmu:54611 (Mm), rno:50678 (Rn)
OMIM 123805 (Hs)
Pharos Q14432 (Hs)
UniProtKB Q14432 (Hs), Q9Z0X4 (Mm), Q62865 (Rn)
Wikipedia PDE3A (Hs)
Enzyme Reaction Click here for help
EC Number: 3.1.4.17

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ensifentrine Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.4 pIC50 2
⤷ pIC50 9.4 (IC50 4x10-10 M) [2]
Description: Inhibition of PDE3 from human platelets
anagrelide Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.1 – 7.3 pIC50 4-6
⤷ pIC50 7.1 – 7.3 (IC50 8.2x10-8 – 5.4x10-8 M) [4-6]
cilostazol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.7 pIC50 8
⤷ pIC50 6.7 (IC50 2x10-7 M) [8]
milrinone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 – 6.4 pIC50 3,8
⤷ pIC50 6.3 – 6.4 (IC50 4.5x10-7 – 4.4x10-7 M) [3,8]
papaverine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.0 pIC50 10
⤷ pIC50 6.0 (IC50 9.17x10-7 M) [10]
enoximone Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 5.4 pIC50 9
⤷ pIC50 5.4 (IC50 3.8x10-6 M) [9]
Description: Measuring inhibition of human platelet PDE
inamrinone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 4.8 pIC50 7
⤷ pIC50 4.8 (IC50 1.6x10-5 M) [7]
Description: Inhibition of PDE3 purified from human platelets, and therefore assumed to be the PDE3A subtype.
ibudilast Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand 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 [8].

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. Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP. (2006) The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2(2,4,6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one]. J Pharmacol Exp Ther, 318 (2): 840-8. [PMID:16682455]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. Zhang Z, Lu X, Xu J, Rothfuss J, Mach RH, Tu Z. (2011) Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A. Eur J Med Chem, 46 (9): 3986-95. [PMID:21705115]

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