SCR‐7952 is a potent, highly selective methionine adenosyltransferase 2A (MAT2A) inhibitor with IC50 of 18.7 nM, Ki of 14.49 nM, shows MTAP‐null selective antiproliferative activity.
SCR‐7952 is 3.7‐fold more potent than the previously reported MAT2A inhibitor AG-270 (Cat# PC-72638).
SCR‐7952 dose‐dependently reduces cellular SAM levels with IC50 of 1.9 nM in in HCT116 MTAP−/− cells, three‐fold more potent than AG-270 (IC50 5.8 nM).
SCR‐7952 exhibits a potent antiproliferation effect on HCT116 MTAP−/− cells, with IC50 of 34.4 nM after 6‐day treatment, with low‐to‐moderate antiproliferation activity on MTAP‐WT HCT116 parent cells.
SCR‐7952 inhibits the growth of MTAP‐deleted cell lines H838, MIA PaCa‐2, and A549, with IC50 of 4.3, 19.7, and 123.1 nM, respectively, with little to no effect on MTAP WT cell line WI‐38.
SCR‐7952 dysregulates splicing downstream of MAT2A and triggers DNA damage through its impact on PRMT5 activity.
SCR‐7952 at 3.0 mg/kg presented a stronger tumor growth inhibition than that of AG‐270 at 200 mg/kg (TGI 82.9 vs. 52.0%, p < 0.0001) in HCT116 MTAP −/− subcutaneous xenograft mouse model.