Fig 2: Regulation of PRMT5 downstream and splicing events. (A) Immunoblot analysis of SDMA and MAT2A after SCR‐7952 treatment for 96 h, and (B) RT‐PCR of expressions of FANCA and the DI‐containing transcripts after SCR‐7952 or AG‐270 treatment for 72 h in HCT116 WT or MTAP‐deleted cells. The protein grayscale analysis was performed by ImageJ 1.54d, normalized to vinculin.

Fig 3: Synergistic activity of SCR‐7952 in combination with the PRMT5 inhibitor. (A) Drug dose–response curves for proliferation inhibition and (B) Bliss plots showing synergistic effects of the combination of SCR‐7952 and JNJ‐64619178 on HCT116 MTAP −/− cells for 8 days. (C) Immunoblot analysis of SDMA and MAT2A after combination treatment for 96 h, and (D) RT‐PCR of expressions of FANCA and the DI‐containing transcripts after SCR‐7952 treatment for 72 h. (E) Impact of SCR‐7952 and JNJ‐64619178 alone and in combination on tumor growth, (F) body weights, and (G) tumor SDMA levels on HCT116 MTAP −/− tumor‐bearing mice (mean ± SEM, n = 8).

Fig 4: Reduction of SAM and antiproliferation of SCR‐7952 on MTAP‐deleted cells. (A) The reduction in cellular SAM levels after 6 h of treatment with SCR‐7952 in HCT116 MTAP −/− cells. (B) The 6‐day antiproliferative effects of SCR‐7952 in HCT116 MTAP −/− and WT cells, and (C) in MTAP‐deleted cell lines NCI‐H838, MIA PaCa‐2, and A549 cells.