Because of the high levels of plasma-protein binding exhibited by WM-8014, WM-8014 can?t be used in vivo in mice. Development of derivatives of WM-8014 resulted in WM-1119, which has reduced plasma-protein binding.
WM-1119 is a highly potent and selective KAT6A inhibitor, with an IC50 of 0.25 μM for KAT6A in lymphoma cells, the binding KD values of WM-1119 with KAT6A, KAT5 and KAT7 are 2 nM, 2.2 μM, 0.5 μM , respectively[1].