phosphodiesterase 4D | Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs) | IUPHAR Guide to IMMUNOPHARMACOLOGY

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phosphodiesterase 4D

  Target has curated data in GtoImmuPdb

Target id: 1303

Nomenclature: phosphodiesterase 4D

Abbreviated Name: PDE4D

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 - - PDE4D phosphodiesterase 4D
Mouse - - Pde4d phosphodiesterase 4D, cAMP specific
Rat - - Pde4d phosphodiesterase 4D
Previous and Unofficial Names
phosphodiesterase E3 dunce homolog (Drosophila) | cAMP-specific 3',5'-cyclic phosphodiesterase 4D | phosphodiesterase 4D, cAMP specific | phosphodiesterase 4D, cAMP-specific
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
Enzyme Reaction
EC Number:
Activator (Human)
PKA-mediated phosphorylation  [3]
Rank order of affinity (Human)
cyclic AMP >> cyclic GMP

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CDP840 Hs Inhibition 8.1 pKi 7
pKi 8.1 (Ki 7.1x10-9 M) [7]
Description: Inhibition of [3H]-R-rolipram binding to recombinant human PDE4D3 isoenzyme
MK-0359 Hs Inhibition 8.9 pIC50 4
pIC50 8.9 (IC50 1.2x10-9 M) [4]
RS-25344 Hs Inhibition 8.4 pIC50 8
pIC50 8.4 [8]
apremilast Hs Inhibition 7.5 pIC50 9
pIC50 7.5 (IC50 3.3x10-8 M) [9]
Description: Potency against recombinant human PDE4D2 isoform in a TR-FRET assay.
compound 29 [Moslin et al., 2017] Hs Inhibition 7.4 pIC50 5
pIC50 7.4 (IC50 4.3x10-8 M) [5]
Description: Binding affinity calculated be measuring displacement of [3H]cAMP binding to purified recombinant His-Tb-hPDE4D2.
difamilast Hs Inhibition >7.3 pIC50 6
pIC50 >7.3 (IC50 <5x10-8 M) [6]
Description: Measuring inhibition of substrate hydrolysis by the PDE4D3 isoform.
rolipram Hs Inhibition 7.2 pIC50 11
pIC50 7.2 (IC50 6.31x10-8 M) [11]
PDE4 inhibitor 16 Hs Inhibition 6.6 pIC50 12
pIC50 6.6 (IC50 2.4x10-7 M) [12]
Description: Inhibition of enzymatic activity of the recombinant human PDE4D catalytic domain in vitro.
Ro20-1724 Hs Inhibition 6.2 pIC50 11
pIC50 6.2 (IC50 6.31x10-7 M) [11]
CBS-3595 Hs Inhibition 6.1 pIC50 1
pIC50 6.1 (IC50 8x10-7 M) [1]
Description: Determined against the PDE4D3 splice variant.
UFM24 Hs Inhibition 5.4 pIC50 10
pIC50 5.4 (IC50 3.53x10-6 M) [10]
Description: Inhibition of PDE4D2 activity in vitro.
Immunopharmacology Comments
The selective PDE4 inhibitor difamilast has been shown to inhibit PDE4D3 [6]. OPA-15406 is a Phase 2 clinical candidate being investigated as a treatment for atopic dermatitis [2].
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0050852 T cell receptor signaling pathway IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0032729 positive regulation of interferon-gamma production IMP
GO:0032743 positive regulation of interleukin-2 production IMP
GO:0032754 positive regulation of interleukin-5 production IMP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0050852 T cell receptor signaling pathway IMP
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0030593 neutrophil chemotaxis IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0030593 neutrophil chemotaxis IEA


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1. Albrecht W, Unger A, Bauer SM, Laufer SA. (2017) Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases. J. Med. Chem., 60 (13): 5290-5305. [PMID:28613871]

2. Hanifin JM, Ellis CN, Frieden IJ, Fölster-Holst R, Stein Gold LF, Secci A, Smith AJ, Zhao C, Kornyeyeva E, Eichenfield LF. (2016) OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study. J. Am. Acad. Dermatol., 75 (2): 297-305. [PMID:27189825]

3. Houslay MD, Adams DR. (2003) PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization. Biochem. J., 370 (Pt 1): 1-18. [PMID:12444918]

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. Moslin R, Gardner D, Santella J, Zhang Y, Duncia JV, Liu C, Lin J, Tokarski JS, Strnad J, Pedicord D et al.. (2017) Identification of imidazo[1,2-b]pyridazine TYK2 pseudokinase ligands as potent and selective allosteric inhibitors of TYK2 signalling. Medicinal Chemistry Communications, 8: 700-712. DOI: 10.1039/C6MD00560H

6. Okada M, Kato M, Sato N, Uno T, Kitagaki H, Haruta J, Hiyama H, Shibata T. (2007) Oxazole compound and pharmaceutical composition. Patent number: WO2007058338. Assignee: Otsuka Pharmaceutical Co., Ltd.. Priority date: 24/05/2007. Publication date: 15/11/2005.

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. Zhang X, Dong G, Li H, Chen W, Li J, Feng C, Gu Z, Zhu F, Zhang R, Li M et al.. (2019) Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. J. Med. Chem., [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.9b00518 [PMID:31099559]


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How to cite this page

Chen Yan.
Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs): phosphodiesterase 4D. Last modified on 06/06/2019. Accessed on 19/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY,