VTP50469 (VTP 50469, SNDX-50469) is potent, selective, orally active inhibitor of Menin-MLL interaction with Ki of 104 pM.
VTP50469 treatment led to a profound reduction in cell proliferation in a concentration-dependent manner in MLL-r cell lines carrying but not in those with WT MLL (HL-60, REH, K562, murine MOZ-TIF2).
VTP50469 treatment rapidly suppresses MLL-fusion target gene expression, induces global changes in Menin and selective changes in MLL chromatin occupancy.
VTP50469 treatment can eradicate disease in PDX models of MLL-r acute leukemia.
