MS33 is a highly effective degrader of the WDR5 protein, exhibiting Kd values of 870 nM and 120 nM for VCB and WDR5, respectively. It induces degradation of WDR5 through an E3 ligase VHL-mediated and proteasome-dependent mechanism. MS33 holds promise for furthering research in the field of acute myeloid leukemia.

VCB:870 nM (Kd), WDR5:120 nM (Kd)

MS33, at concentrations ranging from 0.05 to 5 μM over an 18-hour period, triggers a concentration-dependent degradation of WDR5 in MV4;11 cells[1]. Through Western Blot Analysis, it was established that the degradation of WDR5 by MS33 in MV4;11 cells is both concentration- and time-dependent across various concentrations (0.05, 0.1, 0.5, 1, 5 μM) and incubation times (1, 2, 4, 8, 16, 24 hours). This analysis revealed that MS33 has a DC50 of 260 nM and achieves a maximum degradation efficiency of 71%.