AVN944

AVN-944 (VX-944) is a selective, noncompetitive inhibitor of the enzyme directed against human IMPDH with Ki of 6-10 nM for IMPDH1/IMPDH2. (In Vitro) :AVN-944 (0-1 μM, 48 h) inhibits growth of human multiple myeloma (MM) cell lines in a dose-dependent manner.AVN-944 (800 nM, 0-72 h) induces apoptosis in MM cell lines via a caspase-independent, Bax/AIF/Endo G pathway.AVN-944 (0-200 nM) enhances the cytotoxicity of Doxorubicin (HY-15142A) and Melphalan (HY-17575) .AVN-944 inhibits the proliferation of the human MV-4-11 and murine Ba/F3-Flt3-ITD-dependent cell lines with IC50 values of 26 and 30 nM, respectively.AVN-944 (0-32 μM, 48 h) shows good activity against arenavirus infection at low doses (7.5 μM) with less cytotoxicity.AVN-944 (0-6.4 μM, 48 h) does not reduce the viability of peripheral blood mononuclear cells (PBMNCs) . (In Vivo) :AVN-944 (0-150 mg/kg, Orally, twice daily) significantly increases the median survival time of leukemia model mice.