MZ1

MZ1 is a cell penetrant Proteolysis Targeting Chimera (PROTAC) compound based on (+)-JQ1 conjugated to a von Hippel-Lindau (VHL) ligand. It retains high affinity for BRD2, BRD3 and BRD4 bromodomains (Kd = 13-60 nM) but induces preferential degradation of BRD4 over BRD2 and BRD3. (DC50 values for degradation of BRD4 are 8 and 23 nM in H661 and H838 cells, respectively). MZ1 exhibits potent cytotoxicity and anti-proliferative effects in AML cell lines (pEC50 = 7.6 in Mv4-11 cells).