WD6305 is an effective and selective METTL3-METTL14 PROTAC degrader, with DC50 values of 140 nM and 194 nM for METTL3 and METTL14, respectively. It inhibits m6A modification and the proliferation of acute myeloid leukemia cells while inducing apoptosis. WD6305 also exhibits antitumor activity.

WD6305, within concentrations of 20-5000 nM and over 24 hours, reduces METTL3 protein levels in Mono-Mac-6 cells with a DC50 of 140 nM and a Dmax of 91.9%. Similarly, WD6305 decreases METTL14 protein levels in these cells, achieving a DC50 of 194 nM. Furthermore, at concentrations ranging from 0.5 to 10 μM over 48 hours, WD6305 reduces the m6A/polyA mRNA ratio, inhibits cell proliferation, and induces apoptosis in Mono-Mac-6 cells.