AVN-944 (VX-944) is a potent, selective, noncompetitive inhibitor of both human inosine 5-monophosphate dehydrogenase (IMPDH) isoforms (Ki=6-10 nM).
AVN-944 (VX-944) significantly inhibited the growth of MM cell lines RPMI8226, MM.1S, and U266 cells in a dose-dependent fashion with IC50 of 450, 450, and 600 nM (48h),respectively.
AVN-944 (VX-944) also inhibited growth of drugresistant cell lines, including doxorubicin (Dox)-resistant RPMI8226-Dox40, melphalan (Mel) resistant
RPMI8226-LR5, and Dex (dexamethasone) resistant MM.1R cells, with IC50 values similar to the parental drug-sensitive cell lines.
AVN-944 (VX-944) induced caspase-independent apoptosis in MM cells, induced modest cleavage of caspase 3, 8 and 9, enhances expression of Bax and Bak proteins.
AVN-944 (VX-944) augmented the cytotoxicity of doxorubicin and melphalan even in the presence of BMSCs.
AVN-944 (VX-944) also inhibits ZIKV Replication against ZIKV Paraiba/2015 in A549 cells.