SGC0946

SGC0946 is a selective DOT1L inhibitor with an IC₅₀ value of 0.3 nM. By inhibiting DOT1L, SGC0946 can induce G1 phase arrest, suppress cell self-renewal and metastatic potential, and induce cell differentiation in cancer cells. SGC0946 can be used in the research of tumors such as leukemia and breast cancer, and also serves as a probe to further investigate the cellular mechanisms of DOT1L in normal and diseased cells^[1][2][3]. In Vitro:SGC0946 (0-100 μM; 4 days) inhibits DOT1L with IC₅₀ of 2.65 nM in A431 cells^[1].
SGC0946 (1, 5 μM; 14 days) displays selective reduction of cell viability in an experimental leukaemia model derived from human cord blood cells (transformed with the MLL-AF9 fusion oncogene)^[1].
SGC0946 (1 μM; 3-7 days) shows time- and dose-dependent reductions in the H3K79me2 mark in the Molm13 MLL cell line that has the MLL/AF9 translocation^[1].
SGC0946 (1 μM, 7 days) effectively inhibits MLL target genes, HOXA9 and Meis1^[1].
SGC0946 (0.2, 2, or 20 μM; 12 days) reduces proliferation and survival of ovarian cancer cells by inhibiting DOT1L enzymatic activity^[2].
SGC0946 (10 μM; 12 days) induces G1 phase arrest by blocking DOT1L in SK-OV-3 and TOV21G cells^[2]. In Vivo:SGC0946 (10 mg/kg; i.p.; twice a week for 6 weeks) significantly suppresses tumor progression in a mouse orthotopic xenograft ovarian cancer model and also inhibits DOT1L enzymatic activity and levels of H3K79me2,CDK6, and cyclin D3 in the tumors^[2].