SGC0946

SKU: orb1226099

Description

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

Key Properties

• CAS Number: 1561178-17-3
• MW: 618.57
• Purity: >98% (HPLC)
• Formula: C₂₈H₄₀BrN₇O₄
• SMILES: 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
• Target: HMTase
• Solubility: Ethanol: 100 mg/mL (161.66 mM); DMSO: 100 mg/mL (161.66 mM)

Bioactivity

• 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. 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.
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• In Vitro:
  SGC0946 (0-100 μM; 4 days) inhibits DOT1 L 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 DOT1 L enzymatic activity. SGC0946 (10 μM; 12 days) induces G1 phase arrest by blocking DOT1 L in SK-OV-3 and TOV21G cells. Cell Viability Assay Cell line: A431 cells. Concentration: 0-100 μM. Incubation time: 4 days. Result: Showed potent inhibitory activity against DOT1 L 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.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SGC-0946 | SGC 0946 | SGC0946.

Quick Database Links

Gene Symbol

HMTase