Fig 2: In vivo effects of SCR‐7952. (A) Tumor volumes and (B) body weights of HCT116 MTAP −/− tumor‐bearing mice treated with SCR‐7952, AG‐270, or vehicle (mean ± SEM, n = 7). (C) The effect of SCR‐7952 on human UGT1A1 in a biochemical assay. (D) The levels of plasma total bilirubin (TBIL), direct bilirubin (DBIL), and unconjugated bilirubin (UBIL) of mice 2 h after the final dose (mean ± SEM, n = 3). p Values were calculated using two‐way ANOVA. ****p < 0.0001.

Fig 3: 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.

Fig 4: 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).