产品说明书

Entinostat

Print
Chemical Structure| 209783-80-2 同义名 : 恩替诺特 (MS-275) ;MS-275;SNDX-275;MS 2275
CAS号 : 209783-80-2
货号 : A122285
分子式 : C21H20N4O3
纯度 : 98%
分子量 : 376.409
MDL号 : MFCD08272435
存储条件：

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(132.83 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+30% PEG 300+water 10 mg/mL

生物活性
靶点

  • HDAC3

    HDAC3, IC50:1.7 μM

  • HDAC1

    HDAC1, IC50:0.51 μM
描述 The inhibition of class I HDACs increases the acetylation of histone proteins, which affects the tertiary chromatin structure and leads to altered expression of genes involved in cell proliferation, apoptosis and differentiation. Thus it makes a key role for inhibition of HDACs in anti-proliferation of tumor cells. Entinostat (MS-275) is a selective HDAC 1/2/3 inhibitor with IC50 values of 0.163, 0.396 and 0.605 μM, respectively[1]. A significant increased level of acetylated histone H3 can be observed in PBMCs treated with 5 nM entinostat for 24h. This hyperacetylation effect can also be observed in total cell extracts from PBMCs and tumor tissues in the mouse B16F10 melanoma models when treated orally with 50 mg/kg/day entinostat in a time-dependent manner. The anti-tumor efficacy of entinostat in vivo was proved in several experimental human tumor models with dose of 40 - 50 mg/kg/day, p.o., including MCF7, MDA-MB231, OVCAR3, HeLa-MaTu, DU145, H460, A549, LXF, HT29, HCT116, CAPAN1, 786-O and SK-Mel28 tumor bearing mice. A lot of gene-expression regulated through HDAC inhibition by entinostat are involved in this anti-tumor efficacy, including up-regulation of p21 in cell cycle, H2B in chromatin, CAECAM5 in cell communication and alpha-Tubulin in cytoskeleton, as well as down-regulation of TNFSF13 in apoptosis, HIF1-alpha in angiogenesis, and CTPS2 in metabolism[2]. Entinostat is in phase III for hormone receptor-positive advanced breast cancer and is in phase II for lung cancer, breast cancer, and Hodgkin lymphoma[3].
作用机制 The crystal structure of the HDAC2-benzamide complex reveals that the entinostat coordinates to the catalytic Zn2+ ion through both the carbonyl and amino groups to form an unusual 7-membered ring chelate complex[4].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
697 Growth Inhibition Assay IC50=0.09976 μM SANGER
8-MG-BA Growth Inhibition Assay IC50=1.28866 μM SANGER
A101D Growth Inhibition Assay IC50=0.403 μM SANGER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03280563 Breast Neoplasms Phase 1 Phase 2 Recruiting October 7, 2022 -
NCT02623751 Breast Cancer Phase 1 Active, not recruiting February 2019 Japan ... 展开 >> Chikusa-ku, Aichi, Japan Chuo-ku, Osaka, Japan Chuo-ku, Tokyo, Japan 收起 <<
NCT00823290 Hepatocellular Carcinoma Phase 1 Unknown December 2010 Germany ... 展开 >> Department of Medicine 1, University Hospital Erlangen Recruiting Erlangen, Germany, 91054 Contact: Matthias Ocker, MD    +49-6421-58 ext 68931    Matthias.Ocker@staff.uni-marburg.de    Contact: Susanne Gahr, MD    +49-9131-85 ext 35000    susanne.gahr@uk-erlangen.de    Principal Investigator: Deike Strobel, MD 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.66mL

0.53mL

0.27mL

13.28mL

2.66mL

1.33mL

26.57mL

5.31mL

2.66mL
参考文献

[1]Gao S, Zang J, et al. Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups. Bioorg Med Chem. 2017 Jun 15;25(12):2981-2994.

[2]Hess-Stumpp H, Bracker TU, et al. MS-275, a potent orally available inhibitor of histone deacetylases--the development of an anticancer agent. Int J Biochem Cell Biol. 2007;39(7-8):1388-405. Epub 2007 Feb 16.

[3]Yoon S, Eom GH, et al. HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases. Chonnam Med J. 2016 Jan;52(1):1-11.

[4]Lombardi PM, Cole KE, et al. Structure, mechanism, and inhibition of histone deacetylases and related metalloenzymes. Curr Opin Struct Biol. 2011 Dec;21(6):735-43.

[5]Vendetti FP, Topper M, et al. Evaluation of azacitidine and entinostat as sensitization agents to cytotoxic chemotherapy in preclinical models of non-small cell lung cancer. Oncotarget. 2015 Jan 1;6(1):56-70.

[6]Saito A, Yamashita T, et al. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4592-7.

[7]Yang X, Zhang Q, et al. Pharmacokinetic interaction of entinostat and lapatinib following single and co-oral administration in rats. Xenobiotica. 2014 Nov;44(11):1009-13.