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Verdinexor (KPT-335)

SINE inhibitor, potent and selective CAS# 1392136-43-4

Verdinexor (KPT-335)

Catalog No. BCC5573----Order now to get a substantial discount!

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Quality Control of Verdinexor (KPT-335)

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Chemical structure

Verdinexor (KPT-335)

3D structure

Chemical Properties of Verdinexor (KPT-335)

Cas No. 1392136-43-4 SDF Download SDF
PubChem ID 71492799 Appearance Powder
Formula C18H12F6N6O M.Wt 442.32
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble in DMSO > 10 mM
Chemical Name (Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-N'-pyridin-2-ylprop-2-enehydrazide
SMILES C1=CC=NC(=C1)NNC(=O)C=CN2C=NC(=N2)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F
Standard InChIKey OPAKEJZFFCECPN-XQRVVYSFSA-N
Standard InChI InChI=1S/C18H12F6N6O/c19-17(20,21)12-7-11(8-13(9-12)18(22,23)24)16-26-10-30(29-16)6-4-15(31)28-27-14-3-1-2-5-25-14/h1-10H,(H,25,27)(H,28,31)/b6-4-
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Verdinexor (KPT-335) Dilution Calculator

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Verdinexor (KPT-335) Molarity Calculator

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Preparing Stock Solutions of Verdinexor (KPT-335)

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.2608 mL 11.304 mL 22.6081 mL 45.2161 mL 56.5202 mL
5 mM 0.4522 mL 2.2608 mL 4.5216 mL 9.0432 mL 11.304 mL
10 mM 0.2261 mL 1.1304 mL 2.2608 mL 4.5216 mL 5.652 mL
50 mM 0.0452 mL 0.2261 mL 0.4522 mL 0.9043 mL 1.1304 mL
100 mM 0.0226 mL 0.113 mL 0.2261 mL 0.4522 mL 0.5652 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on Verdinexor (KPT-335)

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.

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References on Verdinexor (KPT-335)

Verdinexor (KPT-335), a Selective Inhibitor of Nuclear Export, Reduces Respiratory Syncytial Virus Replication In Vitro.[Pubmed:30541831]

J Virol. 2019 Feb 5;93(4). pii: JVI.01684-18.

Respiratory syncytial virus (RSV) is a leading cause of hospitalization of infants and young children, causing considerable respiratory disease and repeat infections that may lead to chronic respiratory conditions such as asthma, wheezing, and bronchitis. RSV causes approximately 34 million new episodes of lower respiratory tract illness (LRTI) in children younger than 5 years of age, with >3 million hospitalizations due to severe RSV-associated LRTI. The standard of care is limited to symptomatic relief as there are no approved vaccines and few effective antiviral drugs; thus, a safe and efficacious RSV therapeutic is needed. Therapeutic targeting of host proteins hijacked by RSV to facilitate replication is a promising antiviral strategy as targeting the host reduces the likelihood of developing drug resistance. The nuclear export of the RSV M protein, mediated by the nuclear export protein exportin 1 (XPO1), is crucial for RSV assembly and budding. Inhibition of RSV M protein export by leptomycin B correlated with reduced RSV replication in vitro In this study, we evaluated the anti-RSV efficacy of Verdinexor (KPT-335), a small molecule designed to reversibly inhibit XPO1-mediated nuclear export. KPT-335 inhibited XPO1-mediated transport and reduced RSV replication in vitro KPT-335 was effective against RSV A and B strains and reduced viral replication following prophylactic or therapeutic administration. Inhibition of RSV replication by KPT-335 was due to a combined effect of reduced XPO1 expression, disruption of the nuclear export of RSV M protein, and inactivation of the NF-kappaB signaling pathway.IMPORTANCE RSV is an important cause of LRTI in infants and young children for which there are no suitable antiviral drugs offered. We evaluated the efficacy of KPT-335 as an anti-RSV drug and show that KPT-335 inhibits XPO1-mediated nuclear export, leading to nuclear accumulation of RSV M protein and reduction in RSV levels. KPT-335 treatment also resulted in inhibition of proinflammatory pathways, which has important implications for its effectiveness in vivo.

Description

Verdinexor (KPT-335) is an orally bioavailable, selective XPO1/CRM1 inhibitor.

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