KPT-330
(Synonyms: 塞利尼索) 目录号 : GC12467
KPT-330是CRM1抑制剂，口服生物利用性和选择性
Cas No.:1393477-72-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1, 2]: | |
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Cell lines |
NSCLC cells lines (A549, H460, H1975, PC14, H1299, and H23); MiaPaCa-2 and L3.6pl cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. 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 |
1.0 μmol/L for 24h; or 0.1-1.0 μmol/L |
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Applications |
KPT-330 inhibited proliferation, induced cell cycle arrest and apoptosis-related proteins in 11 NSCLC cells lines (A549, H460, H1975, PC14, H1299, and H23). Moreover, KPT-330 (0.1-1.0 μmol/L) dose-dependently inhibited the growth of MiaPaCa-2 and L3.6pl cells. |
| Animal experiment [1, 2]: | |
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Animal models |
Human NSCLC H1975 tumor xenograft model; human metastatic pancreatic cancer cells are orthotopically injected into the pancreas of mice model |
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Dosage form |
10 mg/kg, oral treatment, thrice weekly for 4 weeks; or 10, 20 mg/kg p.o., 3/week |
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Applications |
KPT-330(10 mg/kg) showed antitumour activity against human non-small cell lung cancer. Moreover, KPT-330 potentiated the antitumor activity of gemcitabine in human pancreatic cancer through inhibition of tumor growth, induction of apoptosis, and depletion of the antiapoptotic proteins. |
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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. Sun, H., Hattori, N., Chien, W., Sun, Q., Sudo, M., GL, E. L., Ding, L., Lim, S. L., Shacham, S., Kauffman, M., Nakamaki, T. and Koeffler, H. P. (2014) KPT-330 has antitumour activity against non-small cell lung cancer. Br J Cancer. 111, 281-291 2. Kazim, S., Malafa, M. P., Coppola, D., Husain, K., Zibadi, S., Kashyap, T., Crochiere, M., Landesman, Y., Rashal, T., Sullivan, D. M. and Mahipal, A. (2015) Selective Nuclear Export Inhibitor KPT-330 Enhances the Antitumor Activity of Gemcitabine in Human Pancreatic Cancer. Mol Cancer Ther. 14, 1570-1581 |
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KPT-330, analog of KPT-185, is a selective inhibitor of CRM1 [1].
Chromosomemaintenance protein 1 (CRM1) is a nuclear export receptor involved in the active transport of transcription factors, cell-cycle regulators, tumor suppressors and RNA molecules. In cancer, CRM1 is overexpression and overactive transport [1].
KPT-330 is an orally bioavailable and selective CRM1 inhibitor. In kidney cancer (RCC) cells, KPT-330 inhibited CRM1 and increased nuclear localization of p21. Then, KPT-330 induced apoptosis and inhibited cells growth [2]. In human non-small cell lung cancer (NSCLC) cells, KPT-330 inhibited cell proliferation and induced the expression of apoptosis-related proteins and cell cycle arrest [3].
In mice bearing MiaPaCa-2 xenograft model, KPT-330 (20 mg/kg) significantly inhibited tumor growth without significant toxicity or body weight loss. Also, KPT-330 increased PAR-4, pro-apoptotic Bax, cleaved PARP and caspase-3. These results suggested that KPT-330 induced apoptosis by the activation of PAR-4 signaling [1]. In mice bearing human NSCLC xenografts, KPT-330 significantly inhibited tumor growth [3].
References:
[1].? Azmi AS, Aboukameel A, Bao B, et al. Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. Gastroenterology, 2013, 144(2): 447-456.
[2].? Wettersten HI, Landesman Y, Friedlander S, et al. Specific inhibition of the nuclear exporter exportin-1 attenuates kidney cancer growth. PLoS One, 2014, 9(12): e113867.
[3].? Sun H, Hattori N, Chien W, et al. KPT-330 has antitumour activity against non-small cell lung cancer. Br J Cancer, 2014, 111(2): 281-291.
KPT-330 是 KPT-185 的类似物，是 CRM1 的选择性抑制剂 [1]。
染色体维持蛋白 1 (CRM1) 是一种核输出受体，参与转录因子、细胞周期调节因子、肿瘤抑制因子和 RNA 分子的主动转运。在癌症中，CRM1过度表达和过度活跃转运[1]。
KPT-330 是一种具有口服生物利用度的选择性 CRM1 抑制剂。在肾癌 (RCC) 细胞中，KPT-330 抑制 CRM1 并增加 p21 的核定位。然后，KPT-330 诱导细胞凋亡并抑制细胞生长 [2]。在人非小细胞肺癌（NSCLC）细胞中，KPT-330抑制细胞增殖并诱导凋亡相关蛋白的表达和细胞周期停滞[3]。
在携带 MiaPaCa-2 异种移植模型的小鼠中，KPT-330 (20 mg/kg) 显着抑制肿瘤生长，而没有明显的毒性或体重减轻。此外，KPT-330 增加了 PAR-4、促凋亡 Bax、裂解的 PARP 和 caspase-3。这些结果表明，KPT-330 通过激活 PAR-4 信号转导诱导细胞凋亡 [1]。在携带人 NSCLC 异种移植物的小鼠中，KPT-330 显着抑制肿瘤生长 [3]。
| Cas No. | 1393477-72-9 | SDF | |
| 别名 | 塞利尼索 | ||
| 化学名 | (Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-N'-pyrazin-2-ylprop-2-enehydrazide | ||
| Canonical SMILES | C1=CN=C(C=N1)NNC(=O)C=CN2C=NC(=N2)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F | ||
| 分子式 | C17H11F6N7O | 分子量 | 443.31 |
| 溶解度 | ≥ 15.15mg/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 | 2.2558 mL | 11.2788 mL | 22.5576 mL |
| 5 mM | 0.4512 mL | 2.2558 mL | 4.5115 mL |
| 10 mM | 0.2256 mL | 1.1279 mL | 2.2558 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。