EPZ5676 |
Catalog No.GC12932
One-Click Copy Product Info
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EPZ5676 is a novel, highly potent and selective DOT1L histone methyltransferase inhibitor with a Ki value of less than 80pM and an IC50 of 0.8nM against DOT1L, showing selectivity that is 37,000-fold higher than against other protein methyltransferases.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1380288-87-8
Sample solution is provided at 25 µL, 10mM.
EPZ5676 is a novel, highly potent and selective DOT1L histone methyltransferase inhibitor with a Ki value of less than 80pM and an IC50 of 0.8nM against DOT1L, showing selectivity that is 37,000-fold higher than against other protein methyltransferases[1-2]. EPZ5676 inhibits H3K79 methylation and the expression of MLL fusion target genes. EPZ5676 is used in research related to mixed-lineage leukemia (MLL-rearranged leukemia) [3-4].
In vitro, EPZ5676 (1μM) was used to treat estrogen receptor-positive/HER2-negative breast cancer cells (MCF7) and estrogen receptor-negative/HER2-positive cells (SKBR3) for 15 days. EPZ5676 significantly inhibited the levels of mono-, di-, and trimethylation of histone H3K79, effectively suppressed colony formation in both breast cancer cell lines, induced cell cycle G1 phase arrest and apoptosis, while also activating the interferon signaling pathway and upregulating HLA class I molecule expression[5]. EPZ5676 (0-3μM) was also used to treat HeLa cells, Molm-13 cells, and MV4-11 cells for 72 hours. EPZ5676 resulted in significant inhibition of histone H3K79 dimethylation levels (IC50=7nM), HoxA9 promoter activity (IC50=52nM), and proliferation of MLL-rearranged leukemia cells (IC50=15nM)[6].
In vivo, in a P. acnes/LPS-induced fulminant hepatitis model, EPZ5676 (35mg/kg/day) was administered intraperitoneally to C57BL/6 mice (starting from day 0 after infection, once every two days, for a total of four times). EPZ5676 significantly improved mouse survival, alleviated liver injury and immune cell infiltration, and enhanced the immunosuppressive function of myeloid-derived suppressor cells (MDSCs)[7]. In a TNBC xenograft model, EPZ5676 (50mg/kg) was administered intraperitoneally to tumor-bearing (MDA-MB-468 cells) NSG mice (once every other day, for a total of six times). EPZ5676 significantly reduced the frequency of tumor-initiating cells, inhibited tumor growth and metastasis, and decreased the proportion of ALDH1+ cancer stem cells[8].
References:
[1] Daigle SR, Olhava EJ, Therkelsen CA, et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood. 2013 Aug 8;122(6):1017-25.
[2] Choi HJ, Nguyen MT, Kim B, et al. DOT1L as a Therapeutic Target: Insights into Epigenetic Regulation and Cancer Treatment. Biomol Ther (Seoul). 2025 Nov 1;33(6):924-933.
[3] Annesley CE, Brown P. Novel agents for the treatment of childhood acute leukemia. Ther Adv Hematol. 2015 Apr;6(2):61-79.
[4] Stein EM, Tallman MS. Mixed lineage rearranged leukaemia: pathogenesis and targeting DOT1L. Curr Opin Hematol. 2015 Mar;22(2):92-6.
[5] Yoshido A, Ishiguro K, Kitajima H, et al. DOT1L inhibition exerts the anti-tumor effect by activating interferon signaling in breast cancer cells. Clin Epigenetics. 2025 Nov 26;17(1):201.
[6] Möbitz H, Machauer R, Holzer P, et al. Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach. ACS Med Chem Lett. 2017 Feb 14;8(3):338-343.
[7] Yang W, Yu H, Huang J, et al. Inhibition of Dot1L Alleviates Fulminant Hepatitis Through Myeloid-Derived Suppressor Cells. Cell Mol Gastroenterol Hepatol. 2021;12(1):81-98.
[8] Kurani H, Razavipour SF, Harikumar KB, et al. DOT1L Is a Novel Cancer Stem Cell Target for Triple-Negative Breast Cancer. Clin Cancer Res. 2022 May 2;28(9):1948-1965.
| Cell experiment [1]: | |
Cell lines | MCF7 cells (human ER-positive/HER2-negative breast cancer cell line) and SKBR3 cells (human ER-negative/HER2-positive breast cancer cell line) |
Preparation Method | MCF7 and SKBR3 cells were treated with EPZ5676 (1µM) for up to 15 days, replacing the medium and drug every 3 days. |
Reaction Conditions | 1µM; 6-15 days. |
Applications | EPZ5676 significantly suppressed colony formation and induced cell cycle arrest (G1 arrest in MCF7 cells) and apoptosis in both breast cancer cell lines. EPZ5676 also activated interferon signaling, upregulated HLA class I expression, and induced DNA damage. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice with P. acnes/LPS-induced fulminant hepatitis |
Preparation Method | Mice were intraperitoneally administered EPZ5676 (35mg/kg) on days 0, 2, 4, and 6 after P. acnes priming, followed by LPS injection on day 7 to induce fulminant hepatitis. Mice were monitored for survival and sacrificed for analysis at day 7. |
Dosage form | 35mg/kg; i.p.; Four injections over 6 days. |
Applications | EPZ5676 treatment significantly improved survival rates, attenuated liver injury severity, reduced hepatic granuloma formation, and decreased hepatocyte apoptosis in fulminant hepatitis mice. EPZ5676 also enhanced the immunosuppressive function of myeloid-derived suppressor cells (MDSCs) through epigenetic regulation of the SOCS1-iNOS pathway. |
References: | |
| Cas No. | 1380288-87-8 | SDF | |
| Chemical Name | (2R,3S,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[3-[2-(6-tert-butyl-1H-benzimidazol-2-yl)ethyl]cyclobutyl]-propan-2-ylamino]methyl]oxolane-3,4-diol | ||
| Canonical SMILES | CC(C)N(CC1C(C(C(O1)N2C=NC3=C2N=CN=C3N)O)O)C4CC(C4)CCC5=NC6=C(N5)C=C(C=C6)C(C)(C)C | ||
| Formula | C30H42N8O3 | M.Wt | 562.71 |
| Solubility | ≥ 28.15 mg/mL in DMSO, ≥ 50.3 mg/mL in EtOH with ultrasonic | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7771 mL | 8.8856 mL | 17.7711 mL |
| 5 mM | 355.4 μL | 1.7771 mL | 3.5542 mL |
| 10 mM | 177.7 μL | 888.6 μL | 1.7771 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)