phosphodiesterase 4A | Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs) | IUPHAR/BPS Guide to PHARMACOLOGY

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phosphodiesterase 4A

target has curated data in GtoImmuPdb

Target id: 1300

Nomenclature: phosphodiesterase 4A

Abbreviated Name: PDE4A

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - - PDE4A phosphodiesterase 4A
Mouse - - Pde4a phosphodiesterase 4A, cAMP specific
Rat - - Pde4a phosphodiesterase 4A
Previous and Unofficial Names
DPDE2 | phosphodiesterase E2 dunce homolog (Drosophila) | cAMP-specific 3',5'-cyclic phosphodiesterase 4A | dunce | phosphodiesterase 4A, cAMP-specific
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.1.4.17
Rank order of affinity (Human)
cyclic AMP >> cyclic GMP

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 Parameter Reference
CDP840 Hs Inhibition 8.0 pKi 6
pKi 8.0 (Ki 9.7x10-9 M) [6]
Description: Inhibition of [3H]-R-rolipram binding to recombinant human PDE-4 isoenzyme
rolipram Hs Inhibition 9.0 pIC50 10
pIC50 9.0 (IC50 1x10-9 M) [10]
MK-0359 Hs Inhibition 8.8 pIC50 4
pIC50 8.8 (IC50 1.6x10-9 M) [4]
revamilast Hs Inhibition 8.6 pIC50 2
pIC50 8.6 (IC50 2.69x10-9 M) [2]
YM976 Hs Inhibition 8.3 pIC50 1
pIC50 8.3 (IC50 5.01x10-9 M) [1]
MK-0873 Hs Inhibition 8.2 pIC50 3
pIC50 8.2 (IC50 6x10-9 M) [3]
apremilast Hs Inhibition 7.8 pIC50 8
pIC50 7.8 (IC50 1.4x10-8 M) [8]
Description: Potency against recombinant human PDE4A1A isoform in a TR-FRET assay.
ibudilast Hs Inhibition 7.3 pIC50 5
pIC50 7.3 (IC50 5.4x10-8 M) [5]
RS-25344 Hs Inhibition 7.2 pIC50 7
pIC50 7.2 [7]
Ro20-1724 Hs Inhibition 6.5 pIC50 10
pIC50 6.5 (IC50 3.16x10-7 M) [10]
UFM24 Hs Inhibition 5.1 pIC50 9
pIC50 5.1 (IC50 7.51x10-6 M) [9]
Description: Inhibition of PDE4A1A activity in vitro.
Inhibitor Comments
We have assigned the IC50 value for revamilast obtained from patent WO2006064355A2 to PDE4A, but the assay description in the patent document does not specify the isozyme tested, or the source of the PDE4 used [2].
Immunopharmacology Comments
PDE4 is a drug target, whose inhibition has anti-inflammatory action. PDE4 inhibitors have already entered clinical use, being employed in the treatment of inflammatory skin conditions such as psoriatic arthritis (apremilast) and atopic dermatitis (crisaborole).

References

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1. Aoki M, Kobayashi M, Ishikawa J, Saita Y, Terai Y, Takayama K, Miyata K, Yamada T. (2000) A novel phosphodiesterase type 4 inhibitor, YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one), with little emetogenic activity. J. Pharmacol. Exp. Ther., 295 (1): 255-60. [PMID:10991987]

2. Gharat LA, Gopalan B, Khairatkar-Joshi N. (2006) Novel heterocyclic compounds useful for the treatment of inflammatory and allergic disorders. Patent number: WO2006064355A2. Assignee: Glenmark Pharmaceuticals S.A.. Priority date: 17/12/2004. Publication date: 22/06/2006.

3. Guay D, Boulet L, Friesen RW, Girard M, Hamel P, Huang Z, Laliberté F, Laliberté S, Mancini JA, Muise E et al.. (2008) Optimization and structure-activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: identification of MK-0873, a potent and effective PDE4 inhibitor. Bioorg. Med. Chem. Lett., 18 (20): 5554-8. [PMID:18835163]

4. Huang Z, Dias R, Jones T, Liu S, Styhler A, Claveau D, Otu F, Ng K, Laliberte F, Zhang L et al.. (2007) L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition. Biochem. Pharmacol., 73 (12): 1971-81. [PMID:17428447]

5. Kodimuthali A, Jabaris SS, Pal M. (2008) Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease. J. Med. Chem., 51 (18): 5471-89. [PMID:18686943]

6. Perry MJ, O'Connell J, Walker C, Crabbe T, Baldock D, Russell A, Lumb S, Huang Z, Howat D, Allen R et al.. (1998) CDP840: a novel inhibitor of PDE-4. Cell Biochem Biophys., 29: 113-32. [PMID:9631241]

7. Saldou N, Obernolte R, Huber A, Baecker PA, Wilhelm R, Alvarez R, Li B, Xia L, Callan O, Su C et al.. (1998) Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Cell. Signal., 10 (6): 427-40. [PMID:9720765]

8. Schafer PH, Parton A, Capone L, Cedzik D, Brady H, Evans JF, Man HW, Muller GW, Stirling DI, Chopra R. (2014) Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cell. Signal., 26 (9): 2016-29. [PMID:24882690]

9. Tsai YF, Chu TC, Chang WY, Wu YC, Chang FR, Yang SC, Wu TY, Hsu YM, Chen CY, Chang SH et al.. (2017) 6-Hydroxy-5,7-dimethoxy-flavone suppresses the neutrophil respiratory burst via selective PDE4 inhibition to ameliorate acute lung injury. Free Radic. Biol. Med., 106: 379-392. [PMID:28263828]

10. Wang P, Myers JG, Wu P, Cheewatrakoolpong B, Egan RW, Billah MM. (1997) Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C, and D. Biochem. Biophys. Res. Commun., 234 (2): 320-4. [PMID:9177268]

Contributors

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How to cite this page

Chen Yan.
Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs): phosphodiesterase 4A. Last modified on 03/04/2018. Accessed on 23/05/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1300.