C199 is a PROTAC degrader targeting PRMT4 with a DC50 of 106 nM. It demonstrates high selectivity for PRMT4 compared to other protein arginine methyltransferases. C199 exhibits strong cellular degradation capacity and induces apoptosis in multiple myeloma cell lines. It efficiently eliminates PRMT4 protein through the VHL-proteasome pathway. C199 has a relatively long half-life and shows potent anti-multiple myeloma (MM) activity.

C199 (Compound C199) effectively inhibits the proliferation of myeloma cells at concentrations of 0.001-1 μM over 12 days. It induces dose-dependent apoptosis in NCI-H929 cells at concentrations of 0.007-0.5 μM over 6 days. Additionally, C199 efficiently and selectively degrades PRMT4 protein in NCI-H929 cells at concentrations of 0.01-0.5 μM within 12-72 hours.

C199 (Compound C199) administered at a dose of 40-80 mg/kg intraperitoneally, twice daily for 20 consecutive days, effectively inhibits the growth of multiple myeloma xenografts in BALB/c nude mice and downregulates PRMT4 expression, without significant organ toxicity. At higher doses of 100-1000 mg/kg intraperitoneally, once daily for 14 days, C199 demonstrates a favorable safety profile with a wide therapeutic window in CD1 mice.