161313-45-7Relevant articles and documents
GLYCOMIMETIC ANTAGONISTS FOR BOTH E- AND P-SELECTINGS
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Figure 7A, (2010/02/12)
Compounds and methods are provided for modulating in vivo and in vivo processes mediated by selectin biniding. More specifically, selectin modulators and their use are described, wherein the selectin modulators that modulate (e.g. inhibit or enhance) a selectin-mediated function comprise particular glycomimetics linked to a member of a class of compounds termed BASAs (Benzyl Amino Sulfonic Acids).
Synthesis and Biological Evaluation of a Potent E-Selectin Antagonist
Thonia, Gebhard,Kinzy, Willy,Bruns, Christian,Patton, John T.,Magnani, John L.,Baenteli, Rolf
, p. 4909 - 4913 (2007/10/03)
An early step of the inflammatory response - the rolling of leukocytes on activated endothelial cells - is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialyl Lewisx (sLex) 1 is a ligand for E-, P-, and L-selectin and, therefore, serves as a lead structure to develop analogues which allow the control of acute and chronic inflammation. Here we describe the efficient synthesis (10 linear steps) of the potent sLex mimetic 2. Compared to sLex, compound 2 showed a 30-fold improved affinity in a static, cell-free E-selectin-ligand binding assay (IC50 = 36 μM). These data were confirmed by a marked inhibition in an in vitro cell-cell rolling assay which simulates in vivo conditions (IC50 ca. 40 μM). The assays are predictive for the in vivo efficacy of test compounds as indicated by a marked inhibitory effect of 2 in a thioglycollate induced peritonitis model of acute inflammation in mice (ED50 ca. 15 mg/kg).
