KPT-330
(Synonyms: 塞利尼索) 目录号 : GC12467
KPT-330（Selinexor）是一种具有口服活性的选择性核输出抑制剂（SINE）化合物，抑制核输出蛋白XPO1（又名CRM1）。
Cas No.:1393477-72-9
Sample solution is provided at 25 µL, 10mM.
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KPT-330 (Selinexor) is an orally active selective inhibitor of nuclear export (SINE) compound that inhibits the nuclear export protein XPO1 (also known as CRM1) [1]. KPT-330 covalently binds to the Cys528 site of XPO1, resulting in its irreversible inactivation [2]. KPT-330 can induce apoptosis, has inhibitory activity against various types of cancer cells, and can also enhance the effects of other chemotherapeutic drugs [3].
In vitro, KPT-330 (0-1000 nM) treatment of non-small cell lung cancer (NSCLC) cell lines for 72 h dose-dependently induced growth inhibition, promoted G1 phase arrest and apoptosis, and stimulated the activation of caspase-3 and caspase-9 [4]. KPT-330 (0-1000 nM) treatment of prostate cancer (PCa) cell lines for 72 h dose-dependently induced cell growth inhibition with IC50 values ranging from 43-700nM [5].
In vivo, oral treatment of mice with non-small cell lung cancer with KPT-330 (10 mg/kg) for 4 weeks significantly reduced tumor volume, reduced Ki-67-positive cells, and increased the percentage of TUNEL-positive cells, and this therapy had a synergistic effect with cisplatin [4]. Oral treatment of mice with pancreatic cancer with KPT-330 (20 mg/kg) for 3 weeks significantly reduced the expression of CRM1 protein in tumor samples, induced p27 nuclear staining, and enhanced the expression of the pro-apoptotic protein Bax [6].
References:
[1] Wang A Y, Liu H. The past, present, and future of CRM1/XPO1 inhibitors[J]. Stem cell investigation, 2019.
[2]Houghton P J, Kang M, Reynolds C P, et al. Pediatric Preclinical Testing Program (PPTP) stage 1 evaluation of the XPO1/CRM1 inhibitor KPT-330[J]. AACR (abstract LB-354), 2013.
[3]Liu S, Qiao W, Sun Q, et al. Chromosome region maintenance 1 (XPO1/CRM1) as an anticancer target and discovery of its inhibitor[J]. Journal of Medicinal Chemistry, 2021, 64(21): 15534-15548.
[4]Sun H, Hattori N, Chien W, et al. KPT-330 has antitumour activity against non-small cell lung cancer[J]. British journal of cancer, 2014, 111(2): 281-291.
[5]Gravina G L, Mancini A, Sanita P, et al. KPT-330, a potent and selective exportin-1 (XPO-1) inhibitor, shows antitumor effects modulating the expression of cyclin D1 and survivin in prostate cancer models[J]. BMC cancer, 2015, 15: 1-19.
[6]Kazim S, Malafa M P, Coppola D, et al. Selective nuclear export inhibitor KPT-330 enhances the antitumor activity of gemcitabine in human pancreatic cancer[J]. Molecular cancer therapeutics, 2015, 14(7): 1570-1581.
KPT-330（Selinexor）是一种具有口服活性的选择性核输出抑制剂（SINE）化合物，抑制核输出蛋白XPO1（又名CRM1）[1]。KPT-330与XPO1的Cys528位点共价结合，导致其不可逆失活[2]。KPT-330可诱导细胞凋亡，对各种类型的癌细胞具有抑制活性，还可以增强其他化疗药物的效果[3]。
在体外，KPT-330（0-1000 nM）处理非小细胞肺癌（NSCLC）细胞系72 h，剂量依赖性地诱导了生长抑制，促进G1期阻滞和细胞凋亡，刺激caspase-3和caspase-9的激活[4]。KPT-330（0-1000 nM）处理前列腺癌（PCa）细胞系72 h，剂量依赖性地诱导了细胞生长抑制，IC50值在43-700nM范围内[5]。
在体内，KPT-330（10 mg/kg）通过口服治疗患有非小细胞肺癌的小鼠4周，显著减小了肿瘤体积， 减少Ki-67阳性细胞，增加TUNEL阳性细胞百分比，且该疗法与顺铂具有协同作用[4]。KPT-330（20 mg/kg）通过口服治疗患有胰腺癌的小鼠3周，显著减少了肿瘤样本中CRM1蛋白的表达，诱导了p27核染色，增强了促凋亡蛋白Bax的表达[6]。
Cell experiment [1]: | |
Cell lines | NSCLC cells |
Preparation method | NSCLC cells were seeded (3×103 cells per well) in 96-well plates, treated with different concentrations of KPT-330 (0, 0.1, 1, 10, 100, and 1000 nM, 72 h), and growth inhibition was measured by MTT assay. |
Reaction Conditions | 0-1000 nM ; 72 h |
Applications | KPT-330 (0.1-1000 nM) induced a dose-dependent growth inhibition after 72 h of exposure. |
Animal experiment [2]: | |
Animal models | Female athymic nude mice |
Preparation method | Female athymic nude mice were injected with luciferase-tagged L3.6pl human metastatic pancreatic cancer cells orthotopically into the pancreas. Mice were divided into four treatment groups of 5 animals each: group 1 was treated with vehicle; group 2 was treated with KPT-330 (20 mg/kg p.o., 3/week); group 3 was treated with gemcitabine (100mg/kg i.p., 2/week); and group 4 was treated with KPT-330 (10 mg/kg p.o., 3/week) + gemcitabine (50 mg/kg i.p., 2/week) for 4 weeks. The treatment was initiated 1 week after orthotopic injection of cell lines. |
Dosage form | 20mg/kg; p.o. |
Applications | CRM1 protein expression was significantly depleted after treatment with KPT-330 alone and in combination with gemcitabine, but was not changed with gemcitabine treatment alone. |
References: | |
| 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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| 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 |
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| % 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。
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Quality Control & SDS
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- Purity: >98.00%
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