EPZ-6438
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
EPZ-6438是一种有效的和生物可用的EZH2抑制剂,抑制包含EZH2的人PRC2(polycomb repressive complex 2)的活性,Ki值为2.5 nM。EZH2是PRC2(polycomb repressive complex 2)的催化亚单位,催化组蛋白H3赖氨酸27(H3K27)的甲基化。
EPZ-6438竞争结合EZH2的S-腺苷甲硫氨酸(SAM)结合位点,也可以非竞争结合多肽或核小体底物的结合位点。EPZ-6438选择性地抑制EZH2的活性,比对EZH1的选择性高35倍。研究结果表明,在恶性横纹肌样瘤(MRT)模型中,EPZ-6438介导的EZH2的抑制在几个癌症途径中的协同效应使得EPZ-6438具有强烈的和永久性的抗肿瘤活性。
参考文献:
Sarah K. Knutson1, Natalie M. Warholic, Tim J. Wigle, Christine R. Klaus, Christina J. Allain, Alejandra Raimondi, Margaret Porter Scott, Richard Chesworth, Mikel P. Moyer, Robert A. Copeland, Victoria M. Richon, Roy M. Pollock, Kevin W. Kuntz, and Heike Keilhack. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. PNAS 2013; 110(19): 7922-7927
- 1. Fumiya Moribe, Momoko Nishikori, et al. "Epigenetic suppression of SLFN11 in germinal center B-cells during B-cell development." PLoS One. 2021 Jan 29;16(1):e0237554. PMID:33513156
- 2. Otsuka Y, Nishikori M, et al. "EZH2 inhibitors restore epigenetically silenced CD58 expression in B-cell lymphomas." Mol Immunol. 2020;119:35–45. PMID:31962268
- 3. Anastassiia Vertii, Jianhong Ou, et al. "Two Contrasting Classes of Nucleolus-Associated Domains in Mouse Fibroblast Heterochromatin." bioRxiv. 2018 December 03.
- 4. Jiang S, Zhou H, et al. "The Epstein-Barr Virus Regulome in Lymphoblastoid Cells." Cell Host Microbe. 2017 Oct 11;22(4):561-573.e4. PMID:29024646
- 5. Arifuzzaman S, Das A, et al. "Selective inhibition of EZH2 by a small molecule inhibitor regulates microglial gene expression essential for inflammation." Biochem Pharmacol. 2017 Apr 19. pii: S0006-2952(17)30233-2. PMID:28431938
- 6. Wang H, Tian L, et al. "Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies." Nat Commun. 2017 Apr 21;8:15045. PMID:28429794
- 7. Xia B, Gerstin E, et al. "Transgenerational programming of longevity through E(z)-mediated histone H3K27 trimethylation in Drosophila." Aging (Albany NY). 2016 Nov 25;8(11):2988-3008. PMID:27889707
Physical Appearance | A solid |
Storage | Desiccate at -20°C |
M.Wt | 572.74 |
Cas No. | 1403254-99-8 |
Formula | C34H44N4O4 |
Synonyms | E-7438 |
Solubility | ≥28.64 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
Chemical Name | N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methyl-5-[4-(morpholin-4-ylmethyl)phenyl]benzamide |
SDF | Download SDF |
Canonical SMILES | CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCOCC5 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验: [1] | |
细胞系 |
SMARCB1确实MRT细胞 |
制备方法 |
溶解度有限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
反应条件 |
4-7天 |
实验结果 |
EPZ-6438以浓度依赖性方式降低总H3K27Me3含量。此外,EPZ-6438产生显著抗增殖作用,IC50值在纳摩尔范围内。EPZ-6438引起CD133、DOCK4和PTPRK的表达,并以时间依赖性方式上调CDKN1A、CDKN2A和BIN1的表达。 |
动物实验: [2] | |
动物模型 |
携带EZH2突变淋巴瘤异种移植物的SCID小鼠。 |
给药剂量 |
每8小时1次,每天3次,每12小时一次,一天2次或口服,每天一次,7或28天。 |
实验结果 |
EPZ-6438以剂量依赖性方式降低肿瘤H3K27Me3的水平,EC50为23 nmol/L。在给药七天/停药七天和给药21天/停药7天的2个周期中,EPZ-6438以剂量依赖性方式显示出显著的抗肿瘤作用,除了最低浓度,其余所有EPZ-6438剂量组引起完全的肿瘤消退。 |
注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: 1. Knutson SK, Warholic NM, Wigle TJ et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7922-7. 2. Knutson SK, Kawano S, Minoshima Y et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mol Cancer Ther. 2014 Apr;13(4):842-54. |
描述 | EPZ-6438是一种有效的和选择性的EZH2抑制剂,Ki和IC50值分别为2.5 nM和11 nM。 | |||||
靶点 | EZH2 | |||||
IC50 | 11 nM (Ki=2.5 nM) |
质量控制和MSDS
- 批次: