LLC0424 is a potent, selective, in vivo active NSD2 PROTAC degrader with DC50 of 20 nM, Dmax value of 96% in RPMI-8402 cells.
LLC0424 selectively induces NSD2 degradation in a cereblon- and proteasome-dependent fashion, does not degrade NSD1 and NSD3 as well as CRBN neo-substrates IKZF1, IKZF3, GSPT1, and CK-1α.
LLC0424 causes continuous downregulation of H3K36me2 and growth inhibition of ALL cell lines with NSD2 mutation.
LLC0424 (60 mg/kg, i.p. or i.v.) showed potent NSD2 degradation in both the SEM and 22RV1 xenograft model.
