SGC0946
Based on 13 publication(s) in Google Scholar
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.
For research use only. We do not sell to patients.
- Purity: 99.68%
- CAS No.: 1561178-17-3
- Formula: C28H40BrN7O4
- Molecular Weight:618.57
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
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Publications Citing Use of MedChemExpress (MCE) SGC0946
More- Cancer Res. 2026 Jul 15;86(14):3588-3603. [Abstract]
- Mol Cell. 2021 Oct 7;81(19):4076-4090.e8. [Abstract]
- Nat Commun. 2026 Feb 12;17(1):1214. [Abstract]
- Leukemia. 2026 Mar 25. [Abstract]
- Sci Adv. 2023 Jun 2;9(22):eadc9273. [Abstract]
- Oncogenesis. 2021 Jul 12;10(7):48. [Abstract]
- Elife. 2020 Oct 1;9:e57858. [Abstract]
- Biochem Pharmacol. 2025 Dec;242(Pt 3):117402. [Abstract]
- Mol Carcinog. 2023 Aug;62(8):1119-1135. [Abstract]
- Genes (Basel). 2024 Sep 13;15(9):1206. [Abstract]
- Technol Cancer Res Treat. 2023 Jan-Dec:22:15330338231167249. [Abstract]
- Oncol Lett. 2024 Jul 19;28(3):444. [Abstract]
- Patent. US20180263995A1.
Customer Validation & Images
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Cell Proliferation/Viability Assay
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In Vivo Efficacy Study
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Cell Imaging/Staining
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RT-PCR
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Flow Cytometry
All Histone Methyltransferase Isoforms
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Biological Activity
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DOT1L 0.3 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| A-431 | IC50 |
2.65 nM
Compound: SGC0946
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Downregulation of H3K79 methylation in human A-431 cells incubated for 3 to 4 days by microscopy based analysis
Downregulation of H3K79 methylation in human A-431 cells incubated for 3 to 4 days by microscopy based analysis
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[PMID: 23250418] |
| MCF-10A | IC50 |
8.8 nM
Compound: 37
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Inhibition of DOT1L in human MCF10A cells assessed as reduction of H3K79 level
Inhibition of DOT1L in human MCF10A cells assessed as reduction of H3K79 level
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[PMID: 25406853] |
| MCF-10A | IC50 |
8.8 nM
Compound: SGC0946
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Downregulation of H3K79 methylation in human MCF-10A cells by fluorescence microscopy analysis
Downregulation of H3K79 methylation in human MCF-10A cells by fluorescence microscopy analysis
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[PMID: 23250418] |
| NCI-H460 | IC50 |
36.01 μM
Compound: SGC0946
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Antiproliferative activity against human NCI-H460 cells harboring DOT1L R231Q mutant (unknown origin) (1 to 416 residues) assessed as inhibition of cell proliferation incubated for 72 hrs by CCK-8 assay
Antiproliferative activity against human NCI-H460 cells harboring DOT1L R231Q mutant (unknown origin) (1 to 416 residues) assessed as inhibition of cell proliferation incubated for 72 hrs by CCK-8 assay
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[PMID: 39255403] |
| NCI-H460 | IC50 |
8.83 μM
Compound: SGC0946
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Antiproliferative activity against human NCI-H460 cells harboring wildtype DOT1L (unknown origin) (1 to 416 residues) assessed as inhibition of cell proliferation incubated for 72 hrs by CCK-8 assay
Antiproliferative activity against human NCI-H460 cells harboring wildtype DOT1L (unknown origin) (1 to 416 residues) assessed as inhibition of cell proliferation incubated for 72 hrs by CCK-8 assay
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[PMID: 39255403] |
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A431 cells
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Concentration:0-100 µM
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Incubation Time:4 days
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Result:Showed potent inhibitory activity against DOT1L with IC50 of 2.65 nM in A431 cells.
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Cell Line:Human cord blood cells (transformed with the MLL-AF9 fusion oncogene).
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Concentration:1, 5 µM
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Incubation Time:14 days
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Result:Killed human cord blood cells transformed with an MLL-AF9 fusion oncogene.
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Cell Line:Molm13 MLL cells
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Concentration:1 µM
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Incubation Time:3-7 days
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Result:Reduced H3K79me2 in Molm13 MLL cells in a time- and dose-dependent manner, and a complete inhibition exhibited at day 7.
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Cell Line:SK-OV-3 and TOV21G cells
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Concentration:0.2, 2, or 20 μM
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Incubation Time:12 days
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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.
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Cell Line:SK-OV-3 and TOV21G cells
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Concentration:10 μM
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Incubation Time:12 days
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Result:Induced increased G1 population and decreased S phase and G2/M phase cells in asynchronized SK-OV-3 and TOV21G cells.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female NOD-SCID mice (4-week-old; mouse orthotopic xenograft ovarian cancer model)[2].
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Dosage:10 mg/kg
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Administration:Intraperitoneal injection; twice a week for 6 weeks.
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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.
Chemical Information
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CAS No. 1561178-17-3
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Appearance Solid
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Molecular Weight 618.57
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Formula C28H40BrN7O4
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Color White to yellow
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SMILES
CC(C)(C1=CC=C(C=C1)NC(NCCCN(C[C@@H]2[C@@H](O)[C@@H](O)[C@H](N3C4=C(C(Br)=C3)C(N)=NC=N4)O2)C(C)C)=O)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (13)
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Journal Impact Factor
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Most Recent
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Cancer Res
Targeting DOT1L Reactivates HERV-K to Drive Cell-Autonomous and Paracrine Senescence in Adenocarcinoma of the Esophagogastric Junction. [Abstract]2026 Jul 15;86(14):3588-3603. PMID: 42084229 -
Mol Cell
A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies. [Abstract]2021 Oct 7;81(19):4076-4090.e8. PMID: 34375582 -
Nat Commun
Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]2026 Feb 12;17(1):1214. PMID: 41680175 -
Leukemia
A Perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged acute myeloid leukemia. [Abstract]2026 Mar 25. PMID: 41882099 -
Sci Adv
Gain-of-function mutations in the catalytic domain of DOT1L promote lung cancer malignant phenotypes via the MAPK/ERK signaling pathway. [Abstract]2023 Jun 2;9(22):eadc9273. PMID: 37256945
SGC0946 purchased from MedChemExpress. Usage Cited in: Sci Adv. 2023 Jun 2;9(22):eadc9273. [Abstract]
CCK-8 assay data showing the sensitivity of NCI-H460-DOT1L-WT/R231Q cells to SGC0946 (0.01,.0.1, 1, 10, 100 μM, 6 days).
SGC0946 purchased from MedChemExpress. Usage Cited in: Sci Adv. 2023 Jun 2;9(22):eadc9273. [Abstract]
CDX-bearing mice were treated with vehicle Cisplatin (3 mg/kg, twice per week), Vinorelbine (4 mg/kg, twice per week), or SGC0946 (20 mg/kg, five times per week) through intraperitoneal administration. The graphs show the tumor images and weights, with the tumor inhibition rate.
SGC0946 purchased from MedChemExpress. Usage Cited in: Sci Adv. 2023 Jun 2;9(22):eadc9273. [Abstract]
Crystal violet staining of NCI-H460-DOT1L-WT/R231Q cells treated with SGC0946 (2.5 or 7.5 μM), binimetinib (2.5 or 7.5 μM), or the combination at the same concentrations for 7 to 14 days (top). Comparison of relative colony formation between groups at 7.5 μM drug concentration.
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Oncogenesis
Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis. [Abstract]2021 Jul 12;10(7):48. PMID: 34253709 -
Elife
Functional interrogation of HOXA9 regulome in MLLr leukemia via reporter-based CRISPR/Cas9 screen. [Abstract]2020 Oct 1;9:e57858. PMID: 33001025
SGC0946 purchased from MedChemExpress. Usage Cited in: Elife. 2020 Oct 1;9:e57858. [Abstract]
Q-PCR analysis of the HOXA9P2A-mCherry cells with or without the 6-day treatment of the DOT1L inhibitor SGC0946 by using specific primers targeting the mRNA sequences of mCherry and HOXA9. The correlation of transcription reduction in mCherry and HOXA9 in response to inhibitor–mediated transcription repression was calculated by performing Pearson’s correlation test.
SGC0946 purchased from MedChemExpress. Usage Cited in: Elife. 2020 Oct 1;9:e57858. [Abstract]
Flow cytometry analysis of the HOXA9P2A-mCherry cells treated with DMSO and various dosages of the DOT1L inhibitor SGC0946 (1, 5 μM).
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Biochem Pharmacol
Targeting DOT1L-mediated histone methylation by hesperetin alleviates retinal microvascular endothelial cell dysfunction and diabetic retinopathy. [Abstract]2025 Dec;242(Pt 3):117402. PMID: 41047037 -
Mol Carcinog
PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia. [Abstract]2023 Aug;62(8):1119-1135. PMID: 37144835 -
Genes (Basel)
CHIR99021 and Brdu Are Critical in Chicken iPSC Reprogramming via Small-Molecule Screening. [Abstract]2024 Sep 13;15(9):1206. PMID: 39336797 -
Technol Cancer Res Treat
DOT1L Epigenetically Regulates Autophagy and Mitochondria Fusion in Cell Lines of Renal Cancer. [Abstract]2023 Jan-Dec:22:15330338231167249. PMID: 37365941 -
Oncol Lett
Pan‑cancer analysis on the role of KMT2C expression in tumor progression and immunotherapy. [Abstract]2024 Jul 19;28(3):444. PMID: 39091583 -
Solvent & Solubility
DMSO : 50 mg/mL (80.83 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (3.36 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (3.36 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (279 KB)
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SDS (420 KB)
- English - EN (420 KB)
- Français - FR (420 KB)
- Deutsch - DE (420 KB)
- Norwegian - NO (420 KB)
- Español - ES (420 KB)
- Swedish - SV (420 KB)
- Italian - IT (420 KB)
- Korean - KR (420 KB)
- Portuguese - PT (420 KB)
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Handling Instructions (2659 KB)
References
[1]. Yu W, et al. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun. 2012;3:1288. [Content Brief]
[2]. Zhang X, et al. Prognostic and therapeutic value of disruptor of telomeric silencing-1-like (DOT1L) expression in patients with ovarian cancer. J Hematol Oncol. 2017 Jan 23;10(1):29. [Content Brief]
[3]. Zhang L, et al. Inhibition of histone H3K79 methylation selectively inhibits proliferation, self-renewal and metastatic potential of breast cancer. Oncotarget. 2014 Nov 15;5(21):10665-77. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.6166 mL | 8.0832 mL | 16.1663 mL | 40.4158 mL |
| 5 mM | 0.3233 mL | 1.6166 mL | 3.2333 mL | 8.0832 mL | |
| 10 mM | 0.1617 mL | 0.8083 mL | 1.6166 mL | 4.0416 mL | |
| 15 mM | 0.1078 mL | 0.5389 mL | 1.0778 mL | 2.6944 mL | |
| 20 mM | 0.0808 mL | 0.4042 mL | 0.8083 mL | 2.0208 mL | |
| 25 mM | 0.0647 mL | 0.3233 mL | 0.6467 mL | 1.6166 mL | |
| 30 mM | 0.0539 mL | 0.2694 mL | 0.5389 mL | 1.3472 mL | |
| 40 mM | 0.0404 mL | 0.2021 mL | 0.4042 mL | 1.0104 mL | |
| 50 mM | 0.0323 mL | 0.1617 mL | 0.3233 mL | 0.8083 mL | |
| 60 mM | 0.0269 mL | 0.1347 mL | 0.2694 mL | 0.6736 mL | |
| 80 mM | 0.0202 mL | 0.1010 mL | 0.2021 mL | 0.5052 mL |
SGC0946 Related Classifications
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