Entinostat 选择性，可口服的 HDAC class

Entinostat  (Synonyms: 恩替诺特; MS-275; SNDX-275)

Entinostat 选择性，可口服的 HDAC class I 抑制剂，抑制 HDAC1，HDAC2 和 HDAC3 的 IC₅₀ 分别为 243 nM，453 nM 和 248 nM。

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生物活性    
Entinostat is an oral and selective class I HDAC inhibitor, with IC50s of 243 nM, 453 nM, and 248 nM for HDAC1, HDAC2, and HDAC3, respectively.

体外研究
Binding affinity of Entinostat (MS-275) against HDAC1 and HDAC2 is 282 nM and 156 nM, respectively[1]. Effects of the HDAC inhibitor Entinostat (MS-275) have been examined in human leukemia and lymphoma cells (U937, HL-60, K562, and Jurkat) as well as in primary acute myelogenous leukemia blasts in relation to differentiation and apoptosis. MS-275 displays dose-dependent effects in each of the cell lines. When administered at a low concentration (e.g., 1 μM), MS-275 exhibits potent antiproliferative activity, inducing p21CIP1/WAF1-mediated growth arrest and expression of differentiation markers (CD11b) in U937 cells. Entinostat (MS-275) potently induces cell death, triggering apoptosis in ~70% of cells at 48 h[2].

体内研究
Entinostat (MS-27-275) at 49 mg/kg shows marked antitumor effects against KB-3-1, 4-1St, and St-4 tumor lines, and a moderate effect against Capan-1 tumor. Entinostat at 24.5 mg/kg and 12.3 mg/kg also shows significant effects against these tumors. In addition, oral administration of Entinostat apparently increases the level of histone acetylation in HT-29 tumor xenografts 4-24 h after the administration[3]. MS-275 administration (3.5 mg/kg i.p.) to Experimental autoimmune neuritis (EAN) rats once daily from the appearance of first neurological signs greatly reduces the severity and duration of EAN and attenuated local accumulation of macrophages, T cells and B cells, anddemyelination of sciatic nerves. In addition, MS-275 treatment increases proportion of infiltrated Foxp3+ cells and anti-inflammatory M2 macrophages in sciatic nerves of EAN rats[4].

分子量    
376.41

性状    
Solid

Formula    
C21H20N4O3

CAS 号    
209783-80-2

中文名称    
恩替诺特

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : 50 mg/mL (132.83 mM; ultrasonic and warming and heat to 60°C)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.6567 mL    13.2834 mL    26.5668 mL
5 mM    0.5313 mL    2.6567 mL    5.3134 mL
10 mM    0.2657 mL    1.3283 mL    2.6567 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

Solubility: ≥ 2.5 mg/mL (6.64 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 2.08 mg/mL (5.53 mM); Clear solution

3.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: ≥ 2.08 mg/mL (5.53 mM); Clear solution

4.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 2.08 mg/mL (5.53 mM); Clear solution
 

参考文献

[1]. Lauffer BE, et al. Histone deacetylase (HDAC) inhibitor kinetic rate constants correlate with cellular histone acetylation but not transcription and cell viability. J Biol Chem. 2013 Sep 13;288(37):26926-43.  [Content Brief] [2]. Rosato RR, et al. The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1. Cancer Res. 2003 Jul 1;63(13):36  [Content Brief] [3]. Saito A, 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, 96(8), 4592-4597.  [Content Brief] [4]. Zhang ZY, et al. MS-275, an histone deacetylase inhibitor, reduces the inflammatory reaction in rat experimental autoimmune neuritis. Neurosci, 2010, 169, 370-377.  [Content Brief]