Verdinexor (KPT-335)

製品コードS7707 バッチS770702

印刷

化学情報

Chemical Structure Synonyms ATG-527 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H12F6N6O
分子量 442.32 CAS No. 1392136-43-4
Solubility (25°C)* 体外 DMSO 88 mg/mL (198.95 mM)
Ethanol 2 mg/mL warmed with 50ºC water bath (4.52 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Verdinexor (KPT-335, ATG-527) is an orally bioavailable, selective XPO1/CRM1 inhibitor.
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]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Jurkat , OCI-Ly3, OCI-Ly10, and CLBL1 cell lines; primary DLBCL cells
濃度 ~10 μM
反応時間 72 or 92 hours
実験の流れ

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.
動物実験 動物モデル Mice with mouse-adapted influenza virus strain A/California/04/09 (pH1N1) or A/Philippines/2/82-X79 (H3N2).
投薬量 25 mg/kg twice daily
投与方法 p.o.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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