Merimepodib is a novel noncompetitive inhibitor

VX-497 has antiproliferative effect on lymphoid and keratinocyte cells. The antiproliferative effect of VX-497 in cells is reversed within 48 h of its removal[1]. VX-497 has intermediate antiviral activity against a second group of viruses, which includes HSV-1, parainfluenza-3 virus, BVDV, VEEV, and dengue virus, with IC50s ranging from 6 to 19 μM. VX-497 is 100-fold more potent, with an IC50 of 380 nM and a corresponding CC50 of 5.2 μM, for a therapeutic index of 14. The antiviral activity of VX-497 in HepG2.2.2.15 cells is reversed threefold by the addition of guanosine.

Oral administration of VX-497 inhibits the primary IgM antibody response in a dose-dependent manner, with an ED50 value of appr 30-35 mg/kg in mice. Single daily dosing of VX-497 is observed to be as effective as twice-daily dosing in this model of immune activation[1]. GVHD developed in the vehicle-treated allografted F1 mice and treatment with VX-497 improved all manifestations of the disease significantly. The 2.9-fold increase in spleen weight in allografted animals is reduced to a 1.6-fold increase in the VX-497-treated mice. Serum IFN-gamma levels are increased 54-fold in the vehicle group while there is a 7.4-fold increase in VX-497-treated animals.

The murine fibroblast L929 cell line is cultured in Eagle minimal essential medium supplemented with 10% fetal bovine serum, nonessential amino acids, 50 U of penicillin per mL, 50 μg of streptomycin per mL, and 2 mM l-glutamine. EMCV is infected at 500 PFU/107 L929 cells. Cells are left untreated or are treated with different concentrations of murine IFN-α alone, VX-497 alone, or combinations thereof.


No corresponding comment