| References: |
CYM-5442 is a highly-selective S1P1 (Spingosine 1-Phosphate Receptor 1) agonist that activates S1P1-dependent pathways in vitro and to levels of full efficacy in vivo through a hydrophobic pocket, separable from the orthosteric site of S1P binding that is headgroup dependent. This is a different site from those involved in the activities of other agonists such as FTY720 and SEW2871.CYM-5442 significantly inhibited but did not prevent aGVHD. CYM-5442 did not affect the infiltration of the donor T cells into the target organs, while the number of macrophages in GVHD organs was significantly reduced by CYM-5442 treatment. In vivo proliferation assays showed that the proliferation of macrophages was not suppressed by CYM-5442. Further studies using human endothelial cells demonstrated that CYM-5442 treatment downregulated CCL2 and CCL7 expression in endothelial cells, therefore reducing the migration of monocytes, from which tissue macrophages originate. Our data demonstrate the therapeutic efficacy of an S1P1-selective agonist in aGVHD and its possible mechanism of action. The results suggest that further investigations are needed regarding CYM-5442 as a potential therapeutic regimen for aGVHD. For the detailed information of CYM5442, the solubility of CYM5442 in water, the solubility of CYM5442 in DMSO, the solubility of CYM5442 in PBS buffer, the animal experiment (test) of CYM5442, the cell expriment (test) of CYM5442, the in vivo, in vitro and clinical trial test of CYM5442, the EC50, IC50,and affinity,of CYM5442, For the detailed information of CYM5442, the solubility of CYM5442 in water, the solubility of CYM5442 in DMSO, the solubility of CYM5442 in PBS buffer, the animal experiment (test) of CYM5442, the cell expriment (test) of CYM5442, the in vivo, in vitro and clinical trial test of CYM5442, the EC50, IC50,and affinity,of CYM5442, Please contact DC Chemicals. |
