(A) Compound 15 reduced the PRMT5 protein level in MCF-7 cells in a PRMT5-, E3 ligase VHL-, and proteasome-dependent manner. MCF-7 cells were treated with 5 μM of compound 15 for 7 d. During the last 24 h, the cells were co-treated with 100 μM VH-298, 2 μM MLN4924, 30 μM MG-132, or 30 μM EPZ015666. The protein levels of PRMT5 were detected by western blotting. (B) PRMT5 degradation induced by compound 15 was reversible. MCF-7 cells were treated with 5 μM of compound 15 for 6 d, and compound 15 was then washed out. The PRMT5 protein levels were detected by western blotting at 0, 12, 24, and 48 h post the washout.