Entinostat (MS-275,SNDX-275)是一种强效的、可口服的组蛋白去乙酰化酶（HDACs）抑制剂，对HDAC1和HDAC3的IC₅₀分别为0.368µM和0.501µM，但对HDAC8的抑制作用相对较弱。
Cas No.:209783-80-2
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Entinostat (MS-275,SNDX-275) is a potent, orally available inhibitor of histone deacetylases (HDACs), with IC₅₀ values of 0.368µM for HDAC1 and 0.501µM for HDAC3, but exhibits relatively weak inhibition of HDAC8[1]. HDACs are associate with a number of well characterized cellular oncogenes and tumor suppressor genes. Entinostat exhibits anti-proliferative activity in vitro in many different human cancer cell lines including breast, colon, lung, myeloma, ovary, pancreas, prostate and leukemia in vivo antitumor activity and also demonstrates antitumor activity in vivo in animal models[1]. Entinostat has been used in preclinical studies for cancer treatment[2].
In vitro, Entinostat (0.1-100µM; 24-72h) inhibited the proliferation of human Y79 and Weri-Rb1 cells in a dose- and time-dependent manner, with GI₅₀ values of 1.34 and 0.98µM for Y79 and Weri-Rb1 cells, respectively, at 72h[3].
In vivo, Entinostat (20mg/kg; i.p.) administered every other day for 21 days reduced ocular tumor burden by 76% in LHh-Tag mice[3]. Entinostat (20mg/kg; i.p.) administered every other day for 13 days reduced ocular tumor burden by 63% in the rat ocular xenograft model[3]. Entinostat (3.5mg/kg; i.p.) administered for 5 days greatly reduced the severity and duration of experimental autoimmune neuritis (EAN), attenuated the local accumulation of macrophages, T cells, and B cells, as well as demyelination of the sciatic nerves, in rats with EAN induced by the neuritogenic synthetic P2 peptide[4].
References:
[1] Hess-Stumpp, Holger et al. “MS-275, a potent orally available inhibitor of histone deacetylases--the development of an anticancer agent.” The international journal of biochemistry & cell biology vol. 39,7-8 (2007): 1388-405.
[2] Pili, R et al. “Phase I study of the histone deacetylase inhibitor entinostat in combination with 13-cis retinoic acid in patients with solid tumours.” British journal of cancer vol. 106,1 (2012): 77-84.
[3] Dalgard, Clifton Lee et al. “Evaluation of the in vitro and in vivo antitumor activity of histone deacetylase inhibitors for the therapy of retinoblastoma.” Clinical cancer research : an official journal of the American Association for Cancer Research vol. 14,10 (2008): 3113-23.
[4] Zhang, Z Y et al. “MS-275, an histone deacetylase inhibitor, reduces the inflammatory reaction in rat experimental autoimmune neuritis.” Neuroscience vol. 169,1 (2010): 370-7.
Entinostat (MS-275,SNDX-275)是一种强效的、可口服的组蛋白去乙酰化酶（HDACs）抑制剂，对HDAC1和HDAC3的IC₅₀分别为0.368µM和0.501µM，但对HDAC8的抑制作用相对较弱[1]。HDACs 与许多已明确特征的细胞癌基因和肿瘤抑制基因有关。Entinostat在体外对许多不同的人类癌细胞系，包括乳腺癌、结肠癌、肺癌、骨髓瘤、卵巢癌、胰腺癌、前列腺癌和白血病，显示出抗增殖活性，在动物模型中也显示出抗肿瘤活性[1]。Entinostat已用于癌症治疗的临床前研究中[2]。
体外实验中，Entinostat（0.1-100µM；24-72h）以剂量依赖和时间依赖的方式抑制人Y79和Weri-Rb1细胞的增殖，在72 h时，其对Y79和Weri-Rb1细胞的IC₅₀值分别为1.34和0.98µM[3]。
体内实验中，Entinostat（20mg/kg；i.p.）每隔一天给药，连续21天，使LHh-Tag转基因小鼠眼部肿瘤负荷降低76%[3]。Entinostat（20mg/kg；i.p.）每隔一天给药，连续13天，使大鼠眼异种移植模型的眼部肿瘤负荷降低63%[3]。在神经源性合成P2肽诱导的实验性自身免疫性神经炎（EAN）大鼠中，给予Entinostat（3.5mg/kg；i.p.）5天，可显著降低神经炎严重程度和持续时间，减轻巨噬细胞、T细胞和B细胞的局部积聚，以及坐骨神经脱髓鞘[4]。
| Cell experiment [1]: | |
Cell lines | Human Y79 and Weri-Rb1 cells |
Preparation Method | For colorimetric analysis, cells were exposed to WST-8 Cell Proliferation Reagent, and absorbance was quantified after 2h using a SpectraMax microplate reader |
Reaction Conditions | 0.1-100µM; 24-72h |
Applications | Entinostat inhibited the proliferation of human Y79 and Weri-Rb1 cells in a dose- and time-dependent manner. |
| Animal experiment [1]: | |
Animal models | LHh-Tag mice |
Preparation Method | LHh-Tag mice were treated every other day for 21d with 20mg/kg Entinostat or DMSO vehicle only (i.p.). Mice were monitored daily and weighed thrice weekly. Animals were sacrificed on day 23, and eyes were enucleated, fixed, and processed to obtain sections from five levels throughout each eye. Tumor burden per mouse was expressed as the mean tumor area per level in both eyes. |
Dosage form | 20mg/kg; every other day for 21d; i.p. |
Applications | Throughout the treatment period, mean body weight of MS-275-treated and control animals did not differ significantly. At treatment end point, Entinostat–treated animals showed a significant, 76% reduction in ocular tumor burden relative to controls. |
References: | |
| Cas No. | 209783-80-2 | SDF | |
| 别名 | 恩替诺特; MS-275; SNDX-275 | ||
| 化学名 | pyridin-3-ylmethyl N-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]carbamate | ||
| Canonical SMILES | C1=CC=C(C(=C1)N)NC(=O)C2=CC=C(C=C2)CNC(=O)OCC3=CN=CC=C3 | ||
| 分子式 | C21H20N4O3 | 分子量 | 376.4 |
| 溶解度 | ≥ 18.8mg/mL in DMSO, ≥ 7.4 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.6567 mL | 13.2837 mL | 26.5675 mL |
| 5 mM | 531.3 μL | 2.6567 mL | 5.3135 mL |
| 10 mM | 265.7 μL | 1.3284 mL | 2.6567 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet