MS159 is a potent PROTAC degrader targeting the nuclear receptor binding SET structural domain protein 2 (NSD2), which inhibits tumor cell growth. This compound serves as a valuable chemical tool for investigating NSD2's function in health and disease [1].

MS159, administered at concentrations ranging from 0.5 to 10 μM over 48 hours, triggers the time- and dose-dependent degradation of NSD2 protein in 293FT cells, which is a reversible process [1]. At a concentration of 2.5 μM and after 72 hours, MS159 not only induces NSD2 degradation, but also effectively degrades IKZF1 and IKZF3 in KMS11 and H929 multiple myeloma cell lines; this degradation is facilitated by the ubiquitin-proteasome system (UPS-) and cereblon (CRBN-) mechanisms [1]. Further, sustained treatment of MS159 (2.5 μM for 8 days) significantly hampers the growth of these multiple myeloma cells, which is attributed to the induced degradation of NSD2 [1].