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KPT-330

现货
Catalog No.
B1464
CRM1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
¥ 680.00
现货
50mg
¥ 3,990.00
现货

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Background

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt443.31
Cas No.1393477-72-9
FormulaC17H11F6N7O
Solubility≥15.15mg/mL in DMSO
Chemical Name(Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-N'-pyrazin-2-ylprop-2-enehydrazide
SDFDownload SDF
Canonical SMILESC1=CN=C(C=N1)NNC(=O)C=CN2C=NC(=N2)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F
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, 2]:

细胞系

人源非小肺癌细胞(A549、H460、H1975、PC14、H1299和H23); 人源胰腺癌细胞(MiaPaCa-2 与L3.6pl)

溶解方法

该化合物在DMSO中的溶解度> 10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃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℃可放置数月。

反应时间

1.0 μmol/L处理24h; 或0.1-1.0 μmol/L

应用

KPT-330处理11种人源非小肺癌细胞(A549、H460、H1975、PC14、H1299和H23),抑制细胞增殖、诱导细胞周期阻滞与凋亡相关蛋白的表达。同时KPT-330 (0.1-1.0 μmol/L) 以剂量相关的方式抑制胰腺癌细胞(MiaPaCa-2 与L3.6pl) 生长。

动物实验 [1, 2]:

动物模型

人源非小肺癌细胞(H1975)异种移植小鼠肿瘤模型;人源胰腺癌细胞原位注射到小鼠胰腺模型

剂量

10 mg/kg、口服给药、每周3次、持续4周;或 10、20 mg/kg口服给药、每周3次

应用

P276-00增强多柔比星药物的抗H-460 移植瘤效果。KPT-330(10 mg/kg)显示抑制人源非小肺癌的生长活性;同时,KPT-330增强吉西他滨抗人源胰腺癌活性,其分子机制包括抑制肿瘤生长、诱导细胞凋亡及诱导抗凋亡蛋白的缺失。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

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

质量控制

化学结构

KPT-330