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chalcone 4

Target nature : CXCL12
CAS n° : 152809-69-3
Mecanism of action : interception (binding to CXCL12 inhibits binding to CXCR4 and to CXCR7)
Physico-chemical properties : solubility 5-15 micromolar in physiological medium solubility is improved by BSA (strong binding to plasma proteins) log D: 3,4 in physiological medium
Probe availability : request to Laboratoire d'innovation thérapeutique (UMR 7200 CNRS-unistra)
Princeps reference : Hachet-Haas M., Balabanian K., Rohmer F., Pons F., Franchet C., Lecat S., Chow KYC, Dagher R., Gizzi P., Didier B., Lagane B., Kellenberger E., Bonnet D., Baleux F., Haiech J., Parmentier M., Frossard N., Arenzana-Seisdedos F., Hibert M, Galzi J.-L.(2008) Small neutralizing molecules to inhibit actions of the chemokine CXCL12. J. Biol. Chem. Vol. 283, 23189-23199.
More bibliography : Chow, K.Y.C., Brotin, E., Ben Khalifa Y., Carthagena, L., Teissier, S., Danckaert, A., Galzi, J.L., Arenzana-Seisdedos, F., Thierry, F. and Bachelerie, F. (2010), functional interplay between human papillomavirus (HPV) and the CXCL12-signaling axis in transformation of keratinocytes. Cell Host&Microbes Volume 8, Issue 5, 523-533 Bouchery T., Dénécé, G., Attout, T., Eberhard, K., Lhermitte-Vallarino, N., Galzi, J.L., Bachelerie, F., Brotin E., Gavotte, L., Moulia, C., Bain, O., Martin, C. (2012) The development and the survival of the filaria Litomosoides sigmodontis in mouse is dependent on the CXCL12/CXCR4 axis. PLOS one;7(4):e34971. Epub 2012 Apr 12. Daubeuf, F.*, Hachet-Haas, M.*, Gizzi, P., Gasparik, V., Bonnet, D., Hibert, M., Frossard, N., Galzi, JL. (*equal first authors) (2013). antedrugs of the chemokine CXCL12 neutraligand show selectivity in an in vivo model of asthma J. Biol. Chem. 288, 11865-11876
Other available information on the probe : poor solubility hampers drug administration (I.P. is OK, other routes are more risky) Chalcone 4 is prone to Michael addition
Other information on the target : CXCR4 is a receptor that palys important roles in development, immune system in child and adult. It bind chemokines, but also danger signals.
Selectivity profile : waek interaction with IL-8 (CXCL8), no interaction with C-C chemokines.
In vivo data : inhibitor of Th2 response ( allergic asthma and atopic dermatitis) inhibitor or CXCL12 signaling in mouse: this lead to reduced immune response to in lisotomoides parasites (injected in pleural cavity) inhibitor of pulmonary arterial hypertension induced by SuHx in the rat inhibitor of inflammatory hyperalgesia no oral bioavailibility. All effects are detected after i.p. injection.
In vitro data : inhibition of CXCR4 calcium signaling inhibition of CXCR4 internalisation by CXCL12 inhibition of peripheral blood CD4+ cells chemotaxis
Toxicity : No adverse effect after 3 weeks i.p. administration at 100 mg/kg.
Chaine SMILES : COc2cc(/C=C/C(=O)c1ccc(Cl)cc1)ccc2O
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