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HO-3867

现货
Catalog No.
B4970
STAT3抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,100.00
现货
5mg
¥ 1,400.00
现货
25mg
¥ 4,180.00
现货

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Background

HO-3867 is a novel curcumin analog and a selective inhibitor of STAT3. [1]
STAT3 (signal transducer and activator of transcription 3) belongs to the STAT protein family. It mediates various gene expressions for numerous cellular functions, including cell growth, division and apoptosis.
HO-3867 selectively blocked STAT3 phosphorylation, transcription, and DNA binding without inhibiting other STATs proteins. It activated apoptosis in ovarian cancer cells and showed minimal toxicity to healthy cells. [2] HO-3867 also significantly inhibited the proliferation of serum-stimulated SMCs and elevated the phosphorylated and total levels of PTENs in SMCs. [3] By inducing cell cycle arrest and apoptosis, HO-3867 reduced the high levels of pSTAT3 Ser727 in endometrial cancer cells. [4]
In mice tumor xenograft, HO-3867 inhibited the tumor growth without toxic side effects, it also blocked PSTAT3/JAK1 and increased apoptotic marker cleaved Caspase 3/PARP. [2] [5] After rat carotid artery injury, HO-3867 inhibited neointima formation and upregulated PTEN expression. [3]
References:
[1] Tierney BJ, McCann GA, Cohn DE, Eisenhauer E, Sudhakar M, Kuppusamy P, Hideg K, Selvendiran K. HO-3867, a STAT3 inhibitor induces apoptosis by inactivation of STAT3 activity in BRCA1-mutated ovarian cancer cells. Cancer Biol Ther. 2012 Jul;13(9):766-75.
[2] Rath KS, Naidu SK, Lata P, Bid HK, Rivera BK, McCann GA, Tierney BJ, Elnaggar AC, Bravo V, Leone G, Houghton P, Hideg K, Kuppusamy P, Cohn DE, Selvendiran K.
HO-3867, a safe STAT3 inhibitor, is selectively cytotoxic to ovarian cancer. Cancer Res. 2014 Apr 15;74(8):2316-27.
[3] Selvendiran K, Kuppusamy ML, Bratasz A, Tong L, Rivera BK, Rink C, Sen CK, Kálai T, Hideg K, Kuppusamy P. Inhibition of vascular smooth-muscle cell proliferation and arterial restenosis by HO-3867, a novel synthetic curcuminoid, through up-regulation of PTEN expression. J Pharmacol Exp Ther. 2009 Jun;329(3):959-66.
[4] Tierney BJ, McCann GA, Naidu S, Rath KS, Saini U, Wanner R, Kuppusamy P,Suarez A, Goodfellow PJ, Cohn DE, Selvendiran K. Aberrantly activated pSTAT3-Ser727 in human endometrial cancer is suppressed by HO-3867, a novel STAT3 inhibitor. Gynecol Oncol. 2014 Oct;135(1):133-41.
[5] Selvendiran K, Tong L, Bratasz A, Kuppusamy ML, Ahmed S, Ravi Y, Trigg NJ, Rivera BK, Kálai T, Hideg K, Kuppusamy P. Anticancer efficacy of a difluorodiarylidenyl piperidone (HO-3867) in human ovarian cancer cells and tumor xenografts. Mol Cancer Ther. 2010 May;9(5):1169-79.

文献引用

1. Tao X, Zuo Q, et al. "Argininosuccinate synthase 1 suppresses cancer cell invasion by inhibiting STAT3 pathway in hepatocellular carcinoma." Acta Biochim Biophys Sin (Shanghai). 2019 Mar 1;51(3):263-276. PMID:30883650

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt464.55
Cas No.1172133-28-6
FormulaC28H30F2N2O2
Solubility≥18.15mg/mL in DMSO
Chemical Name(3E,5E)-3,5-bis(4-fluorobenzylidene)-1-((1-hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl)piperidin-4-one
SDFDownload SDF
Canonical SMILESO=C(/C(CN(CC1=CC(C)(C)N(O[H])C1(C)C)C/2)=C/C3=CC=C(F)C=C3)C2=C\C4=CC=C(F)C=C4
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人上皮卵巢癌细胞系,卵巢癌细胞系SKOV3、OVCAR3、A2780R和OV4

溶解方法

可溶于DMSO。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

10 μmol/L,20 μmol/L,24 h

应用

HO-3867对A2780和其他卵巢癌细胞系具有细胞毒性。HO-3867(20 μmol/L)诱导A2780细胞G2/M细胞周期停滞。HO-3867诱导A2780细胞凋亡。HO-3867诱导凋亡并抑制人卵巢癌细胞株JAK/STAT3信号转导。

动物实验 [1,2]:

动物模型

卵巢癌肿瘤异种移植小鼠模型

给药剂量

25、50和100 ppm,口服

应用

在卵巢癌肿瘤异种移植小鼠中,HO-3867抑制小鼠异种移植肿瘤的生长。在体内,HO-3867抑制pSTAT3并下调STAT3靶蛋白。口服HO-3867(100 ppm)通过降低大鼠肺中的氧化应激和增加PTEN表达来减弱左心衰竭引起的肺动脉高压。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Selvendiran K, Tong L, Bratasz A, et al. Anticancer efficacy of a difluorodiarylidenyl piperidone (HO-3867) in human ovarian cancer cells and tumor xenografts[J]. Molecular cancer therapeutics, 2010, 9(5): 1169-1179.

[2]. Ravi Y, Selvendiran K, Naidu S K, et al. Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung[J]. Hypertension, 2013: HYPERTENSIONAHA. 111.00514.

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