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RGFP966

现货
Catalog No.
A8803
HDAC3抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,000.00
现货
5mg
¥ 900.00
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25mg
¥ 1,800.00
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100mg
¥ 6,120.00
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200mg
¥ 9,000.00
现货

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Background

RGFP966 is a selective inhibitor of HDAC3 with IC50 value of 80 nM [1].

HDAC3 (histone deacetylase 3) is an isoform of HDACs family and plays an important role in DNA transcriptional regulation. It has been shown that HDACs involves in a variety of biologic processes, like DNA repair, replication, transcription and chromatin structure. Many studies have shown that HDACs is the most highly expressed class I HDAC in the brain and involves in learning and memory process negatively [2].

RGFP966 is a potent HDAC3 inhibitor and has no inhibition on other HDACs at the concentration up to 15 μM. Using a substrate-dependent biochemical assay to investigate RGFP966 inhibition of HDACs, and results showed that it inhibited HDAC3 with IC50 value of 80 nM while had no effective inhibition on other HDACs [1]. When tested with cutaneous T cell lymphoma (CTCL) cell lines with RGFP966, the cell growth were significantly decreased by inhibiting HDAC3 which increased cell apoptosis [3].

In male C57BL/6J mice model, trained them in object recognition (ORM) and location-dependent object recognition (OLM) with a subthreshold period after administration of RGFP966 significantly increased the novel object preference and enhanced enhanced long-term OLM in a dose-dependent manner [1].

References:
[1].  Malvaez, M., et al., HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. Proc Natl Acad Sci U S A, 2013. 110(7): p. 2647-52.
[2].  Rogge, G.A., et al., HDAC3 is a negative regulator of cocaine-context-associated memory formation. J Neurosci, 2013. 33(15): p. 6623-32.
[3].  Wells, C.E., et al., Inhibition of histone deacetylase 3 causes replication stress in cutaneous T cell lymphoma. PLoS One, 2013. 8(7): p. e68915.

文献引用

1.Zhang M, Urabe G, et al. "HDAC6 Regulates the MRTF-A/SRF Axis and Vascular Smooth Muscle Cell Plasticity." JACC Basic Transl Sci. 2018 Dec 31;3(6):782-795. PMID:30623138
2.Huang L, Lai WH, et al. "Elimination of HIV-1 Latently Infected Cells by Gnidimacrin and a Selective HDAC Inhibitor." ACS Med Chem Lett. 2018 Feb 6;9(3):268-273. PMID:29541372
3.Topper MJ, Vaz M, et al. "Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer." Cell. 2017 Nov 30;171(6):1284-1300.e21. PMID:29195073
4. Sun XY, Qu Y, et al. "Novel histone deacetylase inhibitor N25 exerts anti-tumor effects and induces autophagy in human glioma cells by inhibiting HDAC3."Oncotarget. 2017 Sep 8;8(43):75232-75242. PMID:29088860

Chemical Properties

StorageStore at -20°C
M.Wt362.4
Cas No.1357389-11-7;1396841-57-8
FormulaC21H19FN4O
SynonymsRGFP 966;RGFP-966
Solubility≥18.12mg/mL in DMSO
SDFDownload SDF
Canonical SMILESC1=CC=C(C=C1)C=CCN2C=C(C=N2)C=CC(=O)NC3=C(C=C(C=C3)F)N
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]:

去乙酰化实验

基于同质荧光释放实验开展去乙酰化实验。将纯化的重组酶与经过梯度稀释的指定浓度抑制剂一起孵育。预孵育时间为0 ~ 3小时,反应在标准HDAC缓冲液中进行。预孵育后,加入乙酰基-赖氨酸 (Ac)-AMC底物(浓度为10 μM,对应于HDAC1和HDAC3的Km值)。上述反应进行1小时。于1小时后,将终浓度为5 mg/mL的胰蛋白酶肽酶显影剂加入,然后使用Tecan M200 96孔读板器测定相应荧光发射。

细胞实验 [2]:

细胞系

HH和Hut78 CTCL细胞

制备方法

在DMSO中的溶解度大于18.1 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C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 °C可放置数月。

反应条件

~ 10 μM;24 ~ 72小时

实验结果

在HH和Hut78 CTCL细胞中,经RGFP966处理24小时能增加H3K9/K14、H3K27和H4K5乙酰化,但对H3K56ac无影响。此外,RGFP966还能增加与DNA损伤以及S期进程紊乱相关的细胞凋亡,从而抑制CTCL细胞生长。

动物实验 [1]:

动物模型

C57BL/6J小鼠

给药剂量

3、10和30 mg/kg;全身给药

实验结果

在ORM训练后,RGFP966呈剂量依赖性地显著增加对新物体的偏好。在亚阈值OLM训练之前或之后的1小时,给予10 mg/kg RGFP966能使小鼠于保留测试期间增加对新物体的偏好,但对物体总探索时间无影响。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Malvaez, M., et al., HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. Proc Natl Acad Sci U S A, 2013. 110(7): p. 2647-52.

[2]. Wells, C.E., et al., Inhibition of histone deacetylase 3 causes replication stress in cutaneous T cell lymphoma. PLoS One, 2013. 8(7): p. e68915.

生物活性

描述 RGFP966是一种特异性的HDAC3抑制剂,IC50值为0.08 μM。
靶点 HDAC3          
IC50 0.08 μM          

质量控制

化学结构

RGFP966

相关生物数据

RGFP966

相关生物数据

RGFP966

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RGFP966