SGC0946

Research use only, not for human use.

SGC0946 is a highly potent and selective DOT1L methyltransferase inhibitor with IC50 of 0.3 nM; selectively kill mixed lineage leukaemia cells.

SGC0946 is a highly potent and selective DOT1L methyltransferase inhibitor with IC50 of 0.3 nM; selectively kill mixed lineage leukaemia cells.

SGC0946 (0-100 μM; 4 days) inhibits DOT1L with IC50 of 2.65 nM in A431 cells.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).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.SGC0946 (1 μM, 7 days) effectively inhibits MLL target genes, HOXA9 and Meis1.SGC0946 (0.2, 2, or 20 μM; 12 days) reduces proliferation and survival of ovarian cancer cells by inhibiting DOT1L enzymatic activity.SGC0946 (10 μM; 12 days) induces G1 phase arrest by blocking DOT1L in SK-OV-3 and TOV21G cells. Cell Viability AssayCell Line:A431 cells Concentration:0-100 μM Incubation Time:4 days Result:Showed potent inhibitory activity against DOT1L with IC50 of 2.65 nM in A431 cells.Cell Viability Assay Cell Line:Human cord blood cells (transformed with the MLL-AF9 fusion oncogene).Concentration:1, 5 μM Incubation Time:14 days Result:Killed human cord blood cells transformed with an MLL-AF9 fusion oncogene.Western Blot Analysis Cell Line:Molm13 MLL cells Concentration:1 μM Incubation Time:3-7 days Result:Reduced H3K79me2 in Molm13 MLL cells in a time- and dose-dependent manner, and a complete inhibition exhibited at day 7.Cell Proliferation Assay Cell Line:SK-OV-3 and TOV21G cells Concentration:0.2, 2, or 20 μM Incubation Time:12 days Result:Inhibited the growth of both SK-OV-3 and TOV21G cells in a dose- and time-dependent manner.Reduced the colony of both SK-OV-3 and TOV21G cells.Cell Cycle Analysis Cell Line:SK-OV-3 and TOV21G cells Concentration:10 μM Incubation Time:12 days Result:Induced increased G1 population and decreased S phase and G2/M phase cells in asynchronized SK-OV-3 and TOV21G cells.

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. Animal Model:Female NOD-SCID mice (4-week-old; mouse orthotopic xenograft ovarian cancer model).Dosage:10 mg/kg Administration:Intraperitoneal injection; twice a week for 6 weeks.Result:Significantly suppressed growth of tumor (size and weight of tumor masses smaller than the untreated group).Inhibited DOT1L enzymatic activity and decreased H3K79me2,CDK6, and cyclin D3 levels in the tumors.

SGC-0946 | SGC 0946 | SGC0946.

Chromatin/Epigenetic

HMTase

DOT1L

Cancer

——

1561178-17-3

618.57

C28H40BrN7O4

>98% (HPLC)

Ethanol: 100 mg/mL (161.66 mM); DMSO: 100 mg/mL (161.66 mM)

O=C(NC1=CC=C(CC(C)C)C=C1)NCCCN(C[C@H]2O[C@@H](N3C=C(Br)C4=C(N)N=CN=C43)[C@H](O)[C@@H]2O)C(C)C

1-(3-((((2R,3S,4R,5R)-5-(4-amino-5-bromo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-isobutylphenyl)urea

(-20℃)

With Ice Pack

≥ 2 years