HO-3867
目录号 : GC16208
A selective STAT3 inhibitor
Cas No.:1172133-28-6
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1]: | |
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Cell lines |
A2780 human epithelial ovarian cancer cell line, ovarian cancer cell lines used (SKOV3, OVCAR3, A2780R, and OV4) |
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Preparation method |
Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
10 μmol/L, 20 μmol/L, 24 h |
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Applications |
HO-3867 was cytotoxic to A2780 and other ovarian cancer cell lines. HO-3867 (20 μmol/L) induced G2 -M cell cycle arrest in A2780 cells. HO-3867 induced apoptosis in A2780 cells. HO-3867 induced apoptosis and inhibited JAK/STAT3 signaling in human ovarian cancer cell lines. |
| Animal experiment [1,2]: | |
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Animal models |
Ovarian cancer tumor xenografted mice model |
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Dosage form |
Oral gavage, 25, 50, and 100 ppm |
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Application |
In ovarian cancer tumor xenografted mice, HO-3867 inhibited the growth of xenograft tumor in mice. HO-3867 inhibited pSTAT3 and downregulated the STAT3-targeting proteins in vivo. HO-3867 (100 ppm p.o.) attenuated left-heart-failure-induced pulmonary hypertension by decreasing oxidative stress and increasing PTEN expression in the lung of rats. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
| Cas No. | 1172133-28-6 | SDF | |
| 化学名 | (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 | ||
| Canonical SMILES | O=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 | ||
| 分子式 | C28H30F2N2O2 | 分子量 | 464.55 |
| 溶解度 | ≥ 18.15mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1526 mL | 10.7631 mL | 21.5262 mL |
| 5 mM | 0.4305 mL | 2.1526 mL | 4.3052 mL |
| 10 mM | 0.2153 mL | 1.0763 mL | 2.1526 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet