Verdinexor (KPT-335)

Catalog No.S7707 Batch:S770701

Technical Data

Formula	C₁₈H₁₂F₆N₆O
Molecular Weight	442.32	CAS No.	1392136-43-4
Solubility (25°C)*	In vitro	DMSO	88 mg/mL (198.95 mM)
		Ethanol	11 mg/mL (24.86 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * 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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Verdinexor (KPT-335, ATG-527) 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 (from reference)

Cell Assay:^{^[1]}	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.
Animal Study:^{^[2]}	Animal Models Mice with mouse-adapted influenza virus strain A/California/04/09 (pH1N1) or A/Philippines/2/82-X79 (H3N2). Dosages 25 mg/kg twice daily Administration p.o.

Cell Assay:^{^[1]}

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.

Animal Study:^{^[2]}

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

References

Selleck's Verdinexor (KPT-335) has been cited by 7 publications

Hepatitis B virus virion secretion is a CRM1-spike-mediated late event [ J Biomed Sci, 2022, 29(1):44]	PubMed: 35729569
CRM1-spike-mediated nuclear export of hepatitis B virus encapsidated viral RNA [ Cell Rep, 2022, 38(10):110472]	PubMed: 35263598
Pancancer transcriptomic profiling identifies key PANoptosis markers as therapeutic targets for oncology [ NAR Cancer, 2022, 4(4):zcac033]	PubMed: 36329783
Effects of cadmium on osteoblast cell line: Exportin 1 accumulation, p-JNK activation, DNA damage and cell apoptosis [ Ecotoxicol Environ Saf, 2021, 208:111668]	PubMed: 33396178
Expression of HIV-1 Intron-Containing RNA in Microglia Induces Inflammatory Responses [ J Virol, 2020, JVI.01386-20]	PubMed: 33298546
A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma [ Cancers (Basel), 2020, 12(11)E3335]	PubMed: 33187254
Transcriptome Profiling of Acquired Gefitinib Resistant Lung Cancer Cells Reveals Dramatically Changed Transcription Programs and New Treatment Targets [ Front Oncol, 2020, 10:1424]	PubMed: 32923394

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SHIPPING AND STORAGE
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