Pinometostat (EPZ5676)
目录号：S7062
Molecular Weight(MW): 562.71
Pinometostat (EPZ5676)是一种蛋白甲基转移酶DOT1L的S-腺苷甲硫氨酸(SAM)竞争性抑制剂，无细胞试验中Ki为80 pM，比作用于所有其他测试的PMTs选择性高37000倍以上，抑制肿瘤中H3K79甲基化。Phase 1。
客户使用Selleck该产品发表文献5篇：
客户使用该产品的5个实验数据：
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Treatment of c-Kit+ bone marrow (BM) cells from Setd2f/f/Vav1-Cre mice with JQ1 500nM, EPZ-5676 1uM, BAY 1143572 400 nM for 24 h. Then cells were collected to determine the proteins levels of RNA pol II (Ser2P), pol II (Ser5P), Gata1, Gata3, Myc, and β-actin by immunoblotting.
Haematologica, 2018, 103(7):1110-1123. Pinometostat (EPZ5676) purchased from Selleck.
(A) HOXA9, PBX3, cleaved caspase 3 and cleaved PARP expression levels in OCI-AML2 and OCI-AML3 cells treated with EPZ5676 (10 µM) and harvested on the indicated day. Three independent western blotting replicates were performed.
Theranostics, 2018, 8(16):4359-4371. Pinometostat (EPZ5676) purchased from Selleck.
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Western blot validation of H3K79me2 depletion in Jurkat cells. Mixtures of 0%–100% EPZ5676-treated cells (0:100; 25:75; 50:50, 75:25; 100:0 proportions of [DMSO-treated:EPZ5676-treated] cells) were measured by immunoblot (IB) for the presence of H3K79me2, H3K4me3, or total histone H3 (loading control). Treated cells were exposed to 20 μM EPZ5676 for 4 days.
Cell Rep, 2014, 9(3): 1163-70 . Pinometostat (EPZ5676) purchased from Selleck.
Dot1l inhibitor decreases IL-6 and IFN-β production triggered by TLR ligands and virus infection. a, b Q-PCR a and ELISA b analysis of the mRNA and protein levels of IL-6 or IFN-β in mouse peritoneal macrophages treated with Dot1l inhibitor EPZ5676 (20 μM) or DMSO for 72 h and then stimulated with LPS (100 ng/ml) or Poly(I:C) (20 μg/ml) for 2 h a or 4 h b, or infected with VSV for 12 h a, b. c ChIP analysis of RNA polymerase II occupancy at the Il6 or Ifnb1 promoters in mouse peritoneal macrophages treated with Dot1l inhibitor EPZ5676 (20 μM) or DMSO for 72 h and then stimulated with LPS (100 ng/ml) or Poly(I:C) (20 μg/ml) for 2 h or infected with VSV (1 MOI) for 12 h. *P < 0.05; **P < 0.01; ***P < 0.001. Data are from three independent experiments (means ± s.e.m.)
Cell Mol Immunol, 2018, doi: 10.1038/s41423-018-0170-4. Pinometostat (EPZ5676) purchased from Selleck.
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Schematic representation of the drug Pinometostat (EPZ‐5676) treatment. Graphical representation of percentage of cell death following normalization with DMSO‐treated cells in C7, C9, and vector control as assessed by resazurin viability assay following drug treatment using 10 nm EPZ‐5676 at various time points. *P < 0.05, **P < 0.001, ***P < 0.0001, 2‐tailed Student's t test (Red * – HCT116 C7 and Black * – HCT116 C9).
Mol Oncol, 2018, doi:10.1002/1878-0261.12423. Pinometostat (EPZ5676) purchased from Selleck.
产品安全说明书
Histone Methyltransferase抑制剂选择性比较
生物活性
| 产品描述 | Pinometostat (EPZ5676)是一种蛋白甲基转移酶DOT1L的S-腺苷甲硫氨酸(SAM)竞争性抑制剂，无细胞试验中Ki为80 pM，比作用于所有其他测试的PMTs选择性高37000倍以上，抑制肿瘤中H3K79甲基化。Phase 1。 | |||||||||||||||||||||||||||||||||||||
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| 靶点 |
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| 体外研究 |
EPZ-5676减少了MV4-11细胞中H3K79双甲基化，IC50是2.6 nM。EPZ-5676浓度和时间依赖性降低H3K79甲基化，而对其他组蛋白位点无作用，这导致在MLL重排的白血病细胞中抑制的关键靶的MLL基因并选择性的凋亡细胞杀伤。EPZ-5676抑制MLL-AF4重新排列细胞系MV4-11的增殖，IC50为9 nM。 |
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| Cell Data |
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| 体内研究 | 在MLL重排的白血病异种移植模型中，EPZ-5676连续静脉滴注21天后导致剂量依赖性的抗肿瘤活性。在最高剂量为70.5毫克/公斤/天时，肿瘤完全消退后治疗停止，长达32天都没有肿瘤再生长。在EPZ-5676治疗的大鼠中，无显著体重减轻或明显毒性出现。 |
推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)
溶解度 (25°C)
| 体外 | DMSO | 100 mg/mL warmed (177.71 mM) |
|---|---|---|
| Ethanol | 92 mg/mL warmed (163.49 mM) | |
| Water | Insoluble | |
| 体内 |
从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 2% DMSO+30% PEG 300+5% Tween 80+ddH2O |
5mg/mL |
* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。
化学数据
| 分子量 | 562.71 |
|---|---|
| 化学式 | C30H42N8O3 |
| CAS号 | 1380288-87-8 |
| 稳定性 | powder |
| in solvent | |
| 别名 | N/A |
计算器
摩尔浓度计算器
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。
稀释计算器
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )
在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.
分子量计算器
通过输入化合物的化学式来计算其分子量：
注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2
摩尔浓度计算器
临床试验信息
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT03724084 | Recruiting | Acute Myeloid Leukemia|KMT2A Gene Rearrangement | National Cancer Institute (NCI) | January 25 2019 | Phase 1|Phase 2 |
| NCT03724084 | Recruiting | Acute Myeloid Leukemia|KMT2A Gene Rearrangement | National Cancer Institute (NCI) | January 25 2019 | Phase 1|Phase 2 |
| NCT02141828 | Completed | Leukemia|Acute Myeloid Leukemia|Acute Lymphocytic Leukemia|Acute Leukemias | Epizyme Inc.|Celgene Corporation | May 2014 | Phase 1 |
| NCT02141828 | Completed | Leukemia|Acute Myeloid Leukemia|Acute Lymphocytic Leukemia|Acute Leukemias | Epizyme Inc.|Celgene Corporation | May 2014 | Phase 1 |
| NCT01684150 | Completed | Acute Myeloid Leukemia|Acute Lymphoblastic Leukemia|Myelodysplastic Syndrome|Myeloproliferative Disorders | Epizyme Inc.|Celgene | September 2012 | Phase 1 |
| NCT01684150 | Completed | Acute Myeloid Leukemia|Acute Lymphoblastic Leukemia|Myelodysplastic Syndrome|Myeloproliferative Disorders | Epizyme Inc.|Celgene | September 2012 | Phase 1 |
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常见问题及建议解决方法
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问题 1：
Is the vehicle 30% PEG400/0.5% Tween80/5% propylene glycol recommended for in vivo use?
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回答：
S7062 EPZ-5676 in 30% PEG400/0.5% Tween80/5% propylene glycol at 30 mg/ml is a suspension. For injection, 2% DMSO/30% PEG 300/5% Tween 80/ddH2O at 5 mg/ml is suitable.
