CM112 is a potent, selective PRMT1 degrader designed by tethering adamantane to MS023 via a 5-PEG linker, has DC50 of 0.83 uM in MCF-7 cells.
CM112 reduces PRMT1 level in a time-dependent manner.
Cotreatment with the proteasome inhibitor MG132 (0.1 μM or 1 μM) and CM112 (10 μM) effectively prevent the degradation of PRMT1 in MCF-7 cells, aligning with the proteasome-dependent mechanism of HyTDs.
CM112 induces the degradation of post-translational PRMT1 without impairing the processes of genetic transcription and translation.
CM112 is still a potent type I PRMTs (PRMT1/3/4/6) pan inhibitor with IC50 values ranging from 9 nM to 224 nM.
CM112 does not affect protein level of PRMT3/4/6.
CM112 suppressed the proliferation of MCF-7 and MDA-MB-231 cells.
CM112 reduces the stability of orphan receptor TR3, which is a binding partner of PRMT1.
