phosphodiesterase 4B

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

   GtoImmuPdb view: OFF :     Currently no data for phosphodiesterase 4B in GtoImmuPdb

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
BRENDA
CATH/Gene3D
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
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 Units Reference
CDP840 Hs Inhibition 8.1 pKi 5
pKi 8.1 (Ki 8.5x10-9 M) [5]
Description: Inhibition of [3H]-R-rolipram binding to recombinant human PDE4B2 isoenzyme
roflumilast Hs Inhibition 9.4 pIC50 4
pIC50 9.4 [4]
rolipram Hs Inhibition 9.0 pIC50 8
pIC50 9.0 (IC50 1x10-9 M) [8]
apremilast Hs Inhibition 7.4 – 7.6 pIC50 7
pIC50 7.4 – 7.6 (IC50 4.3x10-8 – 2.7x10-8 M) [7]
Description: Potency against recombinant human PDE4B1 and B2 isoforms in a TR-FRET assay.
ibudilast Hs Inhibition 7.2 pIC50 3
pIC50 7.2 (IC50 6.5x10-8 M) [3]
RS-25344 Hs Inhibition 6.5 pIC50 6
pIC50 6.5 [6]
Ro20-1724 Hs Inhibition 6.4 pIC50 8
pIC50 6.4 (IC50 3.98x10-7 M) [8]
CBS-3595 Hs Inhibition 5.7 pIC50 2
pIC50 5.7 (IC50 1.9x10-6 M) [2]
Description: Determined against the PDE4B1 splice variant.
crisaborole Hs Inhibition - - 1
[1]
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 [9].

References

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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. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

How to cite this page

Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs): phosphodiesterase 4B. Last modified on 24/07/2017. Accessed on 21/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1301.