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ACY-241

现货
Catalog No.
B5936
HDAC6抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 1,470.00
现货
25mg
¥ 3,990.00
现货

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Background

ACY-241 is a new, selective and orally available inhibitor of HDAC6 [1][2].

Histone deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from an ε-N-acetyl lysine on a histone, allowing the histones to wrap the DNA more tightly. HDAC6 plays an important role in transcriptional regulation and cell cycle progression.

ACY-241 is a new, selective and orally available HDAC6 inhibitor. In MM and MCL cells, the addition of ACY-241 to either lenalidomide (len) or pomalidomide (pom) resulted in synergistic increases in apoptosis and further reduced the expression of transcription factors MYC and IRF4 [1]. In multiple solid tumor cell lines, combination treatment with ACY-241 and paclitaxel resulted in enhanced inhibition of cell proliferation and increased cell death, compared with either single agent alone [2].

In MM xenograft model, combination treatment with ACY-241 and pomalidomide was well tolerated with no overt toxicity and significantly extended survival [1]. In xenograft models of pancreatic and ovarian cancer, combination treatment with ACY-241 and paclitaxel significantly increased mitotic cells with multipolar spindles. ACY-241 dose-dependently increased α-tubulin hyperacetylation [2].

References:
[1].  Quayle SN, Almeciga-Pinto I, Tamang D, et al. Selective HDAC inhibition by ricolinostat (ACY-1215) or ACY-241 synergizes with IMiD® immunomodulatory drugs in Multiple Myeloma (MM) and Mantle Cell Lymphoma (MCL) cells. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research, 2015, Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5380.
[2].  Huang P, Almeciga-Pinto I, Jordan M, et al. Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models. In: Proceedings of the 2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, Massachusetts. Philadelphia (PA): AACR

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt467.95
Cas No.1316215-12-9
FormulaC24H26ClN5O3
Solubility≥23.4mg/mL in DMSO
Chemical Name(Z)-2-((2-chlorophenyl)(phenyl)amino)-N-((Z)-7-hydroxy-7-(hydroxyimino)heptyl)pyrimidine-5-carbimidic acid
SDFDownload SDF
Canonical SMILESClC1=CC=CC=C1N(C2=NC=C(/C(O)=N/CCCCCC/C(O)=N/O)C=N2)C3=CC=CC=C3
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

细胞实验[1]:

细胞系

A2780卵巢癌细胞

溶解方法

在DMSO中的溶解度>23.4mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0.1、0.3、0.5、1、3μM; 溶于DMSO; 24小时

应用

在A2780卵巢癌细胞中,ACY-241(0.3μM)增加α-微管蛋白的超乙酰化,与微管蛋白去乙酰化酶HDAC6的抑制一致。 仅在1μM以上的剂量下观察到组蛋白H3的超乙酰化,即I类HDAC的靶标。相对于H3K56,ACY-241优先诱导α-微管蛋白的超乙酰化。

动物实验[1]:

动物模型

携带MiaPaCa-2胰腺癌异种移植物的雌性无胸腺裸鼠

剂量

ACY-241:50 mg / kg,每日一次,共5天,随后两天休息,连续三周; 腹腔注射紫杉醇:10mg / kg,连续5天; 腹腔注射

应用

在具有MiaPaCa-2胰腺癌异种移植物的雌性无胸腺裸鼠中,ACY-241(50mg / kg)加紫杉醇(10mg / kg)抑制肿瘤生长,并且不导致体重减轻。作为单一剂量以及与紫杉醇组合时,ACY-241在小鼠中耐受性良好。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Huang P, Almeciga-Pinto I, Jordan M, et al. Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models. In: Proceedings of the 2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, Massachusetts. Philadelphia (PA): AACR

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