Gasparik Vincent, Daubeuf François, Hachet-Haas Muriel, Rohmer François, Gizzi Patrick, Haiech Jacques, Galzi Jean-Luc, Hibert Marcel, Bonnet Dominique, Frossard Nelly
Laboratoire d'Innovation Thérapeutique, UMR 7200 CNRS/Université de Strasbourg , Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch, France.
Biotechnologie et signalisation cellulaire, UMR 7242 CNRS/Université de Strasbourg , ESBS, Bld Sébastien Brant, 67412 Illkirch, France.
ACS Med Chem Lett. 2011 Dec 9;3(1):10-4. doi: 10.1021/ml200017d. eCollection 2012 Jan 12.
Chalcone 4 (compound 1) is a small molecule that neutralizes the CXC chemokine CXCL12 and prevents it from acting on the CXCR4 and CXCR7 receptors. To overcome its poor solubility in aqueous buffers, we designed highly soluble analogues of compound 1, phosphate, l-seryl, and sulfate, all inactive by themselves on CXCL12 but when cleaved in vivo into 1, highly active locally at a low dose in a mouse airway hypereosinophilia model.
查耳酮4（化合物1）是一种小分子，它能中和CXC趋化因子CXCL12，并阻止其作用于CXCR4和CXCR7受体。为克服其在水性缓冲液中溶解度差的问题，我们设计了化合物1的高溶解性类似物，即磷酸盐、L-丝氨酸盐和硫酸盐，它们自身对CXCL12均无活性，但在体内裂解成1后，在小鼠气道嗜酸性粒细胞增多模型中以低剂量局部具有高活性。
