产品说明书

Vorinostat

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	同义名 :	N-羟基-N'-苯基辛二酰胺 ;SAHA;Suberoylanilide hydroxamic acid;MK-0683, MK 0683, MK0683, SAHA, M344, CCRIS 8456, HSDB 7930, Vorinostat, suberoylanilide hydroxamic acid, Zolinza;MK0683
	CAS号 :	149647-78-9
	货号 :	A234507
	分子式 :	C₁₄H₂₀N₂O₃
	纯度 :	98%
	分子量 :	264.32
	MDL号 :	MFCD00945317
	存储条件：	粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月
	溶解度 :	DMSO: 105 mg/mL(397.25 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
	动物实验配方：	IP 2% DMSO+2% Tween80+35% PEG300+water 6 mg/mL clear PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点	HDAC HDAC, IC50:~10 nM
描述	HDACs (Histone deacetylases) are a group of enzymes that remove acetyl groups and regulate the histone tail, protein-DNA interaction, chromatin conformation, and even transcription. There are 18 mammalian HDACs divided into four classes: class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10), class III (sirtuin family: sirt1-sirt7) and class IV (HDAC 11)^[1]. Vorinostat, also called as SAHA or MK0683, is a hydroxamic acid based class I and II HDACs pan inhibitor with IC50 value of 10nM on HDAC1 and 20 nM on HDAC3 (measured by immunoprecipitation–HDAC assays)^[2]. Treatement with 6 μM of vorinostat in SH-SY5Y cells for 1 - 12 hours can increase the acetylation signals of histone H3 and H4 in a time-dependent manner. Vorinostat can induce cell-growth inhibition in SH-SY5Y cell line with IC50 value of 2.5 μM and 10 μM at 72h and 48h, respectively. SILAC-based quantitative MS analysis show that SAHA has a dramatic impact on histone lysine acetylation and butyrylation with strong increase in H3K9ac, H3K27ac, H2BK5bu and H4K12bu of SHSY5Y cells. Vorinostat is clinically approved for cutaneous T-cell lymphoma^[3]. Both of gene expression and function of proteins regulating cell proliferation and cell death pathways are involved in the anticancer effects of SAHA, including TFIIB, Rb, Hsp90, Bcl-2 family, tubulin, HIF-1a, ROS, etc.^[4].
作用机制	Vorinostat, structurally similar to TSA, chelates the zinc ion of HDACs by its hydroxamic group^[5].

细胞研究
细胞系	浓度	检测类型	检测时间	活动说明	数据源
22RV1		Growth Inhibition Assay		IC50=2.59274 μM	SANGER
5637		Growth Inhibition Assay		IC50=2.32129 μM	SANGER
639-V		Growth Inhibition Assay		IC50=3.46057 μM	SANGER

临床研究
NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
NCT00771472	Lymphoma	Phase 1	Completed	-	-
NCT00771472	-		Completed	-	-
NCT01064921	Stage III Squamous Cell Carcin... 展开 >>oma of the Oropharynx Stage IV Squamous Cell Carcinoma of the Oropharynx 收起 <<	Phase 1	Completed	-	United States, Ohio ... 展开 >> The Ohio State University Comprehensive Cancer Center Columbus, Ohio, United States, 43210 收起 <<

实验方案

1mg

5mg

10mg

1 mM

5 mM

10 mM

3.78mL

0.76mL

0.38mL

18.92mL

3.78mL

1.89mL

37.83mL

7.57mL

3.78mL

参考文献

[1]Yoon S, Eom GH, et al. HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases. Chonnam Med J. 2016 Jan;52(1):1-11.

[2]Richon VM, Emiliani S, et al. A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3003-7.

[3]Xu G, Wang J, et al. SAHA regulates histone acetylation, Butyrylation, and protein expression in neuroblastoma. J Proteome Res. 2014 Oct 3;13(10):4211-9.

[4]Marks PA, et al. Discovery and development of SAHA as an anticancer agent. Oncogene. 2007 Feb 26;26(9):1351-6.

[5]Finnin MS, Donigian JR, et al. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature. 1999 Sep 9;401(6749):188-93.

[6]Hrzenjak A, Moinfar F, et al. Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo. Mol Cancer. 2010 Mar 4;9:49.

[7]Akada H, Akada S, et al. Efficacy of vorinostat in a murine model of polycythemia vera. Blood. 2012 Apr 19;119(16):3779-89.

[8]Nidhyanandan S, Thippeswamy BS, et al. Enhanced anticancer efficacy of histone deacetyl inhibitor, suberoylanilide hydroxamic acid, in combination with a phosphodiesterase inhibitor, pentoxifylline, in human cancer cell lines and in-vivo tumor xenografts. Anticancer Drugs. 2017 Oct;28(9):1002-1017.

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靶点

靶点	数值

HDAC	HDAC, IC50:~10 nM