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    Verdinexor (KPT-335)
    Verdinexor (KPT-335)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V1684
    CAS #: 1392136-43-4Purity ≥98%

    Description: This product has been discontinued. Verdinexor (also known as KPT-335) is an orally bioavailable, selective XPO1/CRM1 inhibitor. Verdinexor inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, Verdinexor downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Verdinexor treatment of cell lines upregulated the expression of both protein and mRNA for the tumor suppressor proteins p53 and p21, and promoted their nuclear localization. 

    References: J Virol. 2014 Sep 1;88(17):10228-43; Am J Physiol Renal Physiol. 2014 Dec 1;307(11):F1179-86.

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    Molecular Weight (MW)442.32
    FormulaC18H12F6N6O
    CAS No.1392136-43-4
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 88 mg/mL (199.0 mM)
    Water: <1 mg/mL
    Ethanol: 11 mg/mL (24.86 mM)
    Solubility (In vivo) N/A
    Synonyms KPT-335; KPT335; KPT 335


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    In Vitro

    In vitro activity: Verdinexor inhibits the viability of Jurkat, OCI-Ly3, OCI-Ly10, and CLBL1 cells with IC50 of 0.3 nM, 2.1 nM, 41.8 nM, and 8.5 nM, respectively. KPT-335 also induces apoptosis in CLBL1 cells and primary canine DLBCL cells that express XPO1 and SINE. Verdinexor potently and selectively inhibits vRNP export and effectively inhibits the replication of various influenza virus A and B strains, including pandemic H1N1 virus, highly pathogenic H5N1 avian influenza virus, and the recently emerged H7N9 strain.


    Cell Assay: Cell viability for lymphoid lines is determined by the MTS assay using CellTiter 96® AQueous One Solution Cell Proliferation Assay Kit. Briefly, for lymphoid cell lines, 5×104 cells (or 1×105 primary DLBCL cells) are cultured in 100 µL of complete medium in 96-well plates in the presence of SINE compounds. After 72 hours, 20 µL of MTS solution is added to each well and cells are incubated for another 4 hours before measuring absorbance at 490 nm using a Wallac Victor 1420 Multilabel Counter. The IC50 of SINE is calculated using Prism 6 software. For the non-lymphoid cell lines, 96 well plates are seeded in triplicate in 90 µL with 2500 cells/well of OSA16, 5000 cells/well of C2, and 2500 cells/well of 323610-3. Seeded plates are cultured overnight then treated the following day with 10 µL of KPT-214 in C10 media at concentrations of 0.0001, 0.01, 0.1, 1.0, and 10 µM. Plates are collected at 92 hours, centrifuged at 1300 rpm, and supernatant is removed by inverting plates on absorbent paper. Plates are then sealed and immediately placed at −80°C for a minimum of 12 hours. Plates are then thawed and CyQUANT ®Cell Proliferation Assay is performed following the manufacturer’s protocol. Briefly, 200 µL of the diluted working CyQUANT solution is added to each well and protected from light. Fluorescence is the measured using a SpectraMax M2 microplate reader at 480 nm excitation and 520 nm emission. Results are represented as percent of control, or plotted to calculate IC50 values at 92 hours.

    In VivoVerdinexor (KPT-335) is potent in inhibiting virus shedding, moderating leukocyte infiltration into the bronchoalveolar space, and reducing pulmonary pro-inflammatory cytokine expression in mice. 
    Animal modelBALB/c female mice (6-8 week-old) 
    Formulation & Dosage20 mg/kg every two days; Oral gavage
    References

    J Virol. 2014 Sep 1;88(17):10228-43; Am J Physiol Renal Physiol. 2014 Dec 1;307(11):F1179-86.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    Verdinexor

    Verdinexor, a novel SINE, is efficacious against influenza A and B viruses. J Virol. 2014 Sep 1;88(17):10228-43.
     
     

    Verdinexor

    Verdinexor treatment resulted in nuclear accumulation of vRNP. A549 cells were pretreated for 2 h with DMSO, verdinexor (1 μM), or LMB (10 nM). Cells were infected with influenza virus A/WSN/33 at an MOI of 3 for 8 h. J Virol. 2014 Sep 1;88(17):10228-43.
     

    Verdinexor

    Verdinexor reduces lung influenza A virus burdens. The efficacy of in vivo prophylactic (A to C) and therapeutic (D to F) verdinexor treatment was evaluated. J Virol. 2014 Sep 1;88(17):10228-43.


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