General information
CAS n°
not yet attributed?
Mechanism of action
neutralizes CXCL12 like Chalcone 4
Physico-chemical properties
solubility in buffer= 30 µM
Probe availability
request to Laboratoire d'innovation thérapeutique (UMR 7200 CNRS-unistra)
Princeps reference
Regenass, P., Abboud, D., Daubeuf, F., Riché, S., Marsol, C., Rohmer, F., Hachet-Haas, M., Hibert, M., Frossard, N., Galzi, JL., Bonnet, D. (2018). Structure-Activity Relationship Study toward the Discovery of Novel CXCL12 Neutraligands with in vivo Activity in an Allergic Eosinophilic Airway Inflammation Model. J. Med. Chem. 61(17):7671-7686. doi: 10.1021/acs.jmedchem.8b00657
More bibliography
Bonnet, D., Frossard, N., Galzi, JL., Guignabert, C., Hibert, M., Simonin, F. Muller, S. (2106) Pyrimidinone derivatives and uses thereof to neutralize the biological activity of chemokines13 July 2016. European patent application EP16305908.2
Other available information on the probe
fully inhibits binding of CXCL12 to CXCR4
Other information on the target
x
Selectivity profile
effect on CCL17, CCL22, CCL5, CCL2. other chemokines were not tested.No alert in the safety 44 assay
In vivo data
- orally bioavailable- inhibits eosinophil recruitment in the OVA mouse model of asthma- inhibits hyperalgesia linked to opiates, inflammatory, and neuropathic pain
In vitro data
KD for CXCL12 = 267 +/- 71 nM
Toxicity
no toxicity after 8 d treatment with 350 µmol/kg
Chaine SMILES
COc3cc(c2cc(c1ccc(Cl)cc1)[nH]c(=O)n2)ccc3O