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

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phosphodiesterase 4B

  Target has curated data in GtoImmuPdb

Target id: 1301

Nomenclature: phosphodiesterase 4B

Abbreviated Name: PDE4B

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 - 736 1p31 PDE4B phosphodiesterase 4B
Mouse - 721 4 C6 Pde4b phosphodiesterase 4B, cAMP specific
Rat - 721 5q32 Pde4b phosphodiesterase 4B
Previous and Unofficial Names
DPDE4 | phosphodiesterase E4 dunce homolog (Drosophila) | cAMP-specific 3',5'-cyclic phosphodiesterase 4B | Pde4B1 | Pde4B2 | Pde4B3 | Pde4B4 | phosphodiesterase 4B, cAMP-specific | phosphodiesterase 4B, cAMP specific
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Enzyme Reaction
EC Number:
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 8.5x10-9 M) [7]
Description: Inhibition of [3H]-R-rolipram binding to recombinant human PDE4B2 isoenzyme
roflumilast Hs Inhibition 9.4 pIC50 6
pIC50 9.4 [6]
MK-0359 Hs Inhibition 9.3 pIC50 4
pIC50 9.3 (IC50 5x10-10 M) [4]
rolipram Hs Inhibition 9.0 pIC50 11
pIC50 9.0 (IC50 1x10-9 M) [11]
apremilast Hs Inhibition 7.4 – 7.6 pIC50 9
pIC50 7.4 – 7.6 (IC50 4.3x10-8 – 2.7x10-8 M) [9]
Description: Potency against recombinant human PDE4B1 and B2 isoforms in a TR-FRET assay.
ibudilast Hs Inhibition 7.2 pIC50 5
pIC50 7.2 (IC50 6.5x10-8 M) [5]
RS-25344 Hs Inhibition 6.5 pIC50 8
pIC50 6.5 [8]
Ro20-1724 Hs Inhibition 6.4 pIC50 11
pIC50 6.4 (IC50 3.98x10-7 M) [11]
CBS-3595 Hs Inhibition 5.7 pIC50 2
pIC50 5.7 (IC50 1.9x10-6 M) [2]
Description: Determined against the PDE4B1 splice variant.
UFM24 Hs Inhibition 5.1 pIC50 10
pIC50 5.1 (IC50 8.58x10-6 M) [10]
Description: Inhibition of PDE4B2 activity in vitro.
crisaborole Hs Inhibition - - 1
roflupram N/A Inhibition - - 13
Knocking down the expression of PDE4B in primary microglial cells led to enhanced level of LC-3 II and decreased activation of inflammasome. [13]
View species-specific inhibitor tables
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). PDE4B is the predominant phosphodiesterase subtype in monocytes and neutrophils and this is thought to be the sub-type central to inflammatory action of phosphodiesterases [12]. The development compound difamilast is reported to show selectivity for this PDE4 isoform [3].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0030593 neutrophil chemotaxis ISS
GO:0050900 leukocyte migration ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0001780 neutrophil homeostasis ISS
GO:0050852 T cell receptor signaling pathway IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0032729 positive regulation of interferon-gamma production IMP
GO:0032743 positive regulation of interleukin-2 production IMP
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes
GO:0030593 neutrophil chemotaxis ISS
GO:0050900 leukocyte migration ISS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0050852 T cell receptor signaling pathway IMP
General Comments
PDE4B is the predominant phosphodiesterase subtype in monocytes and neutrophils and this is thought to be the sub-type central to inflammatory action of phosphodiesterases [12].


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1. Akama T, Baker SJ, Zhang YK, Hernandez V, Zhou H, Sanders V, Freund Y, Kimura R, Maples KR, Plattner JJ. (2009) Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg. Med. Chem. Lett., 19 (8): 2129-32. [PMID:19303290]

2. 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]

3. 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]

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. Lunniss CJ, Cooper AW, Eldred CD, Kranz M, Lindvall M, Lucas FS, Neu M, Preston AG, Ranshaw LE, Redgrave AJ et al.. (2009) Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration. Bioorg. Med. Chem. Lett., 19 (5): 1380-5. [PMID:19195882]

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. Wang P, Wu P, Ohleth KM, Egan RW, Billah MM. (1999) Phosphodiesterase 4B2 is the predominant phosphodiesterase species and undergoes differential regulation of gene expression in human monocytes and neutrophils. Mol. Pharmacol., 56 (1): 170-4. [PMID:10385698]

13. You T, Cheng Y, Zhong J, Bi B, Zeng B, Zheng W, Wang H, Xu J. (2017) Roflupram, a Phosphodiesterase 4 Inhibitior, Suppresses Inflammasome Activation through Autophagy in Microglial Cells. ACS Chem Neurosci, 8 (11): 2381-2392. [PMID:28605578]


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