Verdinexor (KPT-335)
(Synonyms: KPT-335) 目录号 : GC15777
An inhibitor of XPO1
Cas No.:1392136-43-4
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Verdinexor (KPT-335) is a potent and selective inhibitor of nuclear export [1].
Nuclear export (SINE) is mainly mediated by exportin 1 (XPO1) and mediates specific proteins out of the nucleus, which plays an important role in the regulation of proliferation and the cell cycle [2].
Verdinexor (KPT-335) is a potent and selective SINE inhibitor that acts as an antiviral drug. In A549 cells inoculated with the influenza A and B virus, verdinexor effectively inhibited the replication of the influenza A and B virus strains tested. verdinexor (1 µM) caused the accumulation of vRNPs in the nuclei and altered the localization of viral NS1. Also, verdinexor increased nuclear negative-sense vRNA by 56.6-fold and significantly reduced cytoplasmic negative-sense vRNA, which suggested that verdinexor blocked vRNP nuclear export. In 293T cells, verdinexor inhibited XPO1-NEP binding [1].
In mice infected with influenza virus A, verdinexor significantly reduced lung influenza virus A titers. Verdinexor also reduced the expression of proinflammatory cytokines tumor necrosis factor alpha, interleukin-6, interleukin-1β and gamma interferon. In mice infected with a lethal dose, verdinexor inhibited virus penetration of the respiratory tract and virus spread in the lungs [1]. In companion dogs with B- and T-cell lymphomas, verdinexor showed potent cytotoxic activity [2].
References:
[1]. Perwitasari O, Johnson S, Yan X, et al. Verdinexor, a novel selective inhibitor of nuclear export, reduces influenza a virus replication in vitro and in vivo. J Virol, 2014, 88(17): 10228-10243.
[2]. Gravina GL, Senapedis W, McCauley D, et al. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol, 2014, 7: 85.
| Cell experiment: | |
|
Cell lines |
Human A549 cells |
|
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. |
|
Reacting condition |
2 h, 1 μM |
|
Applications |
Verdinexor (KPT-335) is a selective and orally available inhibitor of nuclear export. Verdinexor (KPT-335) prevents nuclear export of progeny influenza virus genome and inhibits the replication of multiple influenza viruses, including H1N1, H5N1 and H7N9 influenza virus. Verdinexor (KPT-335) disrupts XPO1-NEP binding, resulting in the blockage of nuclear vRNP export of several influenza A virus[1]. Besides, verdinexor (KPT-335) inhibits proliferation and induces apoptosis of canine melanoma cells[2]. |
| Animal experiment [3]: | |
|
Animal models |
BALB/c female mice (6-8 week-old) |
|
Dosage form |
Oral gavage with 20 mg/kg every two days. |
|
Application |
Verdinexor (KPT-335) is potent in inhibiting virus shedding, moderating leukocyte infiltration into the bronchoalveolar space, and reducing pulmonary pro-inflammatory cytokine expression in mice. |
|
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. |
|
References: [1]. Perwitasari O, Johnson S, Yan X, et al. Verdinexor, a novel selective inhibitor of nuclear export, reduces influenza a virus replication in vitro and in vivo[J]. Journal of virology, 2014, 88(17): 10228-10243. [2]. Breit M N, Kisseberth W C, Bear M D, et al. Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines[J]. BMC veterinary research, 2014, 10(1): 1. [3]. Perwitasari O, Johnson S, Yan X, et al. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection[J]. PloS one, 2016, 11(11): e0167221. | |
| Cas No. | 1392136-43-4 | SDF | |
| 别名 | KPT-335 | ||
| 化学名 | (Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-N'-pyridin-2-ylprop-2-enehydrazide | ||
| Canonical SMILES | C1=CC=NC(=C1)NNC(=O)C=CN2C=NC(=N2)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F | ||
| 分子式 | C18H12F6N6O | 分子量 | 442.32 |
| 溶解度 | ≥ 44.2mg/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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2608 mL | 11.304 mL | 22.6081 mL |
| 5 mM | 0.4522 mL | 2.2608 mL | 4.5216 mL |
| 10 mM | 0.2261 mL | 1.1304 mL | 2.2608 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