DEG-77 is a more soluble analog of DEG-35, dual degrader of IKZF2 and casein kinase 1α (CK1α) with DC50 of 15.3 nM and 10 nM respectively. DEG-77 shows increased selectivity against IKZF2 (DC50 = 15.3 nM) and CK1α (DC50 = 10 nM) over other known neosubstrates (GSPT1, IKZF1, IKZF3). DEG-77 reduced abundance of HOXA9 and c-MYC in MOLM-13 cells. DEG-77 treatment resulting in increased apoptosis, myeloid differentiation, and induction of the TP53 pathway, and comparable preferential sensitivity to leukemia versus healthy cells. DEG-77 has better efficacy and can block leukemic stem cell activity.
