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phosphodiesterase 4C

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1302

Nomenclature: phosphodiesterase 4C

Abbreviated Name: PDE4C

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 - 712 19p13.11 PDE4C phosphodiesterase 4C
Mouse - 686 8 34.15 cM Pde4c phosphodiesterase 4C, cAMP specific
Rat - 536 16p14 Pde4c phosphodiesterase 4C
Previous and Unofficial Names Click here for help
phosphodiesterase E1 dunce homolog (Drosophila) | cAMP-specific 3,5-cyclic phosphodiesterase 4C | phosphodiesterase 4C, cAMP-specific
Database Links Click here for help
Alphafold Q08493 (Hs), Q3UEI1 (Mm), P14644 (Rn)
BRENDA 3.1.4.17
CATH/Gene3D 1.10.1300.10
ChEMBL Target CHEMBL291 (Hs)
DrugBank Target Q08493 (Hs)
Ensembl Gene ENSG00000105650 (Hs), ENSMUSG00000031842 (Mm), ENSRNOG00000019518 (Rn), ENSRNOG00000043249 (Rn)
Entrez Gene 5143 (Hs), 110385 (Mm), 290646 (Rn)
Human Protein Atlas ENSG00000105650 (Hs)
KEGG Enzyme 3.1.4.17
KEGG Gene hsa:5143 (Hs), mmu:110385 (Mm), rno:290646 (Rn)
OMIM 600128 (Hs)
Pharos Q08493 (Hs)
UniProtKB Q08493 (Hs), Q3UEI1 (Mm), P14644 (Rn)
Wikipedia PDE4C (Hs)
Enzyme Reaction Click here for help
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 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
CDP840 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.7 pKi 3
⤷ pKi 7.7 (Ki 1.89x10-8 M) [3]
Description: Inhibition of [3H]-R-rolipram binding to recombinant human PDE4C2 isoenzyme
RS-25344 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 4
⤷ pIC50 8.1 [4]
MK-0359 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 1
⤷ pIC50 8.0 (IC50 9.1x10-9 M) [1]
apremilast Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.9 pIC50 5
⤷ pIC50 6.9 (IC50 1.18x10-7 M) [5]
Description: Potency against recombinant human PDE4C1 isoform in a TR-FRET assay.
ibudilast Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 2
⤷ pIC50 6.6 (IC50 2.39x10-7 M) [2]
rolipram Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.5 pIC50 7
⤷ pIC50 6.5 (IC50 3.16x10-7 M) [7]
6-Hydroxy-5,7-dimethoxyflavone Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.8 pIC50 6
⤷ pIC50 5.8 (IC50 1.75x10-6 M) [6]
Description: Inhibition of PDE4C1 activity in vitro.
Ro20-1724 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.4 pIC50 7
⤷ pIC50 5.4 (IC50 3.98x10-6 M) [7]
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. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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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