切换导航

Rocilinostat (ACY-1215)

现货
Catalog No.
A4083
选择性的HDAC6抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 750.00
现货
5mg
¥ 700.00
现货
10mg
¥ 1,000.00
现货
50mg
¥ 2,660.00
现货
200mg
¥ 8,500.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

Rocilinostat (ACY-1215) is a selective inhibitor of HDAC6 with IC50 of 5 nM [1].
HDAC6 (histone deacetylase 6) is an enzyme which encoded by the HDAC6 gene and plays an important role in translational regulation, cell cycle progression and developmental events. It has been revealed that over-expression of HDAC6 is correlated with tumorigenesis and cell survival and HDAC6 also involves in cancer cells metastasis [2] [3].
Rocilinostat (ACY-1215) is a selective HDAC6 inhibitor. When tested with human MM cell lines (MM.1S), treatment with ACY-1215 in increasing dose for 6 hours increased acetylated α-tubulin at a concentration of 0.62μM via inhibiting HDAC6 [1]. In multiple myeloma cells, used ACY-125 as an adjuvant with carfilzomib triggered synergistic anti-MM effects, even in bortezomib-resistant cells which resulted in enhance cells apoptosis [2].
In mouse model with xenografted human MM cells, administration of ACY-125 only or with bortezomib could markedly delay tumor growth and the combination showed best efficacy [1].
It is also reported that ACY-1215 has minimal activity against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2 (IC50 > 1μM), and has slight activity against HDAC8 (IC50 = 0.1μM) [1]. When tested with mouse xenografted MM cells, combination carfilzomib with ACY-1215 showed a decreased effect on tumor volume and cells apoptosis [2].
References:
[1].    Santo, L., et al., Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood, 2012. 119(11): p. 2579-89.
[2].    Mishima, Y., et al., Ricolinostat (ACY-1215) induced inhibition of aggresome formation accelerates carfilzomib-induced multiple myeloma cell death. Br J Haematol, 2015.
[3].    Haakenson, J., et al., HDAC6-Dependent Functions in Tumor Cells: Crossroad with the MAPK Pathways. Crit Rev Oncog, 2015. 20(1-2): p. 65-81.

文献引用

1.Sun, Yuefeng, et al. "Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation." Scientific reports 5 (2015). PMID:26166158

Chemical Properties

StorageStore at -20°C
M.Wt433.5
Cas No.1316214-52-4
FormulaC24H27N5O3
Solubility≥21.675 mg/mL in DMSO, <2.34 mg/mL in EtOH, <2.04 mg/mL in H2O
Chemical NameN-[7-(hydroxyamino)-7-oxoheptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide
SDFDownload SDF
Canonical SMILESC1=CC=C(C=C1)N(C2=CC=CC=C2)C3=NC=C(C=N3)C(=O)NCCCCCCC(=O)NO
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

激酶实验[1]:

抑制活性

将ACY-1215溶解,随后在实验缓冲液[50 mM HEPES、pH 7.4、100 mMKCl、0.001% Tween-20、0.05% BSA和20 μMtris(2-carboxyethyl)phosphine]中稀释至最终浓度的6倍。使用实验缓冲液将HDAC酶稀释至最终浓度的1.5倍,并在加入底物之前用ACY-1215预孵育10分钟。用于每种酶的FTS(HDAC1、HDAC2、HDAC3和HDAC6)或MAZ-1675(HDAC4、HDAC5、HDAC7、HDAC8和HDAC9)的量等于通过滴定曲线确定的米氏常数。用0.3μM测序级胰蛋白酶将实验缓冲液中的FTS或MAZ-1675稀释至终浓度的6倍。将底物/胰蛋白酶混合物加入到酶/化合物混合物中,振荡60秒,然后置于SpectraMax M5微量滴定板读数器中。在肽底物中赖氨酸侧链去乙酰化后,监测酶反应30分钟内7-amino-4-methoxy-coumarin的释放,并计算反应的线性速率。使用Cerep对HDAC11、sirtuin1和sirtuin2进行测定。

细胞实验 [1]:

细胞系

MM细胞,PBMCs

溶解方法

该化合物在DMSO中的溶解度大于10 mM。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

0.16、0.8、4、20 nM,MM细胞: 24 h, PBMCs: 48 h.

实验结果

在PHA刺激或未刺激的PBMC中,ACY-1215细胞毒性较小。在纯化的CD4+ T细胞中,ACY-1215诱导毒性,IC50值为2.5 μM。在MM细胞系中,ACY-1215以剂量依赖性的方式降低细胞活力,IC50值为2-8 μM,并诱导显著的细胞毒性。在MM.1S细胞中,ACY-1215以剂量依赖性方式降低粘附于BMSCs的MM细胞的DNA合成,并抑制IL-6和IGF-1诱导的生长。

动物实验[1]:

动物模型

MM1S细胞皮下接种的雄性SCID小鼠

剂量

50 mg/kg,一周5天,持续3周,口服

溶解方法

溶于10% DMSO,5% 葡萄糖

实验结果

在人类MM异种移植小鼠模型中,ACY-1215(50 mg/kg)显著延迟肿瘤生长。用ACY-1215和bortezomib共同使用显著延长小鼠总生存期(OS)并诱导多泛素化蛋白的显著积累。用ACY-1215和bortezomib共同使用耐受性良好,对体重没有显著影响。在MM.1S-LucNeo细胞静脉内接种的雌性SCID-beige小鼠中,ACY-1215(75 mg/kg)和bortezomib(1.5 mg/kg)显著抑制肿瘤生长并延长OS。

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]. Santo L, Hideshima T, Kung AL, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood, 2012, 119(11): 2579-2589.

生物活性

描述 Rocilinostat (ACY-1215)是一种选择性的HDAC6抑制剂,非细胞试验中IC50为5 nM。
靶点 HDAC6          
IC50 5 nM          

质量控制

化学结构

Rocilinostat (ACY-1215)

相关生物数据

Rocilinostat (ACY-1215)

相关生物数据

Rocilinostat (ACY-1215)

相关生物数据

Rocilinostat (ACY-1215)