Verdinexor (KPT-335)

Catalog No.S7707

Verdinexor (KPT-335) Chemical Structure

Molecular Weight(MW): 442.32

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

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Purity & Quality Control

Choose Selective CRM1 Inhibitors

Biological Activity

Description Verdinexor (KPT-335) is an orally bioavailable, selective XPO1/CRM1 inhibitor.
Targets
CRM1 [1]
In vitro

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. [1] 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. [2]

In vivo Verdinexor (25 mg/kg twice daily, p.o.) reduces proinflammatory cytokine expression in the lung, produces in vivo antiviral activity by reducing lung virus titers, and thus reduces pulmonary disease pathogenesis and death associated with lethal influenza A virus challenge. [2] In autosomal-dominant polycystic kidney disease model, Verdinexor (5 mg/kg, i.p.) attenuates cyst growth via inhibition of XPO1. [3]

Protocol

Cell Research:

[1]

+ Expand
  • Cell lines: Jurkat , OCI-Ly3, OCI-Ly10, and CLBL1 cell lines; primary DLBCL cells
  • Concentrations: ~10 μM
  • Incubation Time: 72 or 92 hours
  • Method:

    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.


    (Only for Reference)
Animal Research:

[2]

+ Expand
  • Animal Models: Mice with mouse-adapted influenza virus strain A/California/04/09 (pH1N1) or A/Philippines/2/82-X79 (H3N2).
  • Formulation: --
  • Dosages: 25 mg/kg twice daily
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 88 mg/mL (198.95 mM)
Ethanol 11 mg/mL warmed (24.86 mM)
Water Insoluble
In vivo Add solvents individually and in order:
5% DMSO+corn oil
15mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 442.32
Formula

C18H12F6N6O

CAS No. 1392136-43-4
Storage powder
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02431364 Completed Healthy Karyopharm Therapeutics, Inc May 2015 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID