Target nature :
CAS n° :
Mecanism of action :
neutraligand. its binding to CCL22 prevents binding to CCR4
Physico-chemical properties :
highly soluble in water.
GPN 000136 isomerizes to GPN008758 in aqueous medium
Probe availability :
GreenPharma company / Ambinter
Princeps reference :
Abboud, D., Villa, P., Daubeuf, F., Utard, V., Haiech, J., Bonnet, D., Hibert, M., Bernard, P., Galzi, J.L.*, Frossard, N.* (2015) A strategy to discover decoy chemokine ligands with an anti-inflammatory activity, Sci Rep. 2015 Oct 7;5:14746. doi: 10.1038/srep14746
More bibliography :
Abboud D, Hanson J., Chemokine neutralization as an innovative therapeutic strategy for atopic dermatitis.; Drug Discov Today. 2017 Apr;22(4):702-711. doi: 10.1016/j.drudis.2016.11.023. Epub 2016 Dec 9.
Other available information on the probe :
GPN 136 is a derivative of salycilate that has become a type 2 CMR in 2018.
Other information on the target :
CCR4 is expressed on Th2-type helper lymphocytes, eosinophils and dendritic cells.
CCL17, CCL22 and CCR4 contribute to the pathogenesis of atopic diseases, like asthma and atopic dermatitis, as the expression of both ligands and their receptor is enhanced in asthmatic patients and AD skin lesions.
Selectivity profile :
GPN 136 does not affect cellular responses evoked by CCL3, CCL4, CCL5, CCL22, CXCL8, CXCL10, CXCL11 and CXCL12
In vivo data :
in a model of allergic asthma induced by Ovalbumin application GPN 136, administered intraperitoneally at 350 µMol/kg inhibits recruitment of eosinophils in the bronchoalveolar lavage.
In vitro data :
KD for CCL22 is in the range of 50 nM (tryptophan fluorescence assay)
At 10 µM, GPN 136 block 60% of cellular calcium elevation in CCR4-expressing HEK cells
GPN 136 inhibits CCL22-mediated internalisation of CCR4 with IC50 = 1 µM
GPN 136 block CCR4+ HUT78T cells migration invitro with an IC50 value = 3x10-8M
No toxicity has been detected after 2 weeks daily treatment at 350 µMol/kg
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