| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
| Targets |
Exportin 1 (XPO1/CRM1) [1]
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| ln 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. 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. |
| ln Vivo |
Verdinexor (KPT-335) is potent in inhibiting virus shedding, moderating leukocyte infiltration into the bronchoalveolar space, and reducing pulmonary pro-inflammatory cytokine expression in mice.
In vivo, intraperitoneal administration of KPT-335 at 5 mg/kg biweekly for 2 weeks significantly reduced the total kidney weight/body weight ratio in Pkd1v/v mice (control n=7, KPT-335 n=5) [1]. Immunohistochemistry showed a clear reduction in the proliferation marker Ki-67 in treated kidneys versus controls, indicating inhibition of proliferation [1]. Confirmation of on-target effects: p53 showed clear confinement within the nuclei of tubular epithelial cells in the treatment group [1]. |
| Animal Protocol |
20 mg/kg every two days; Oral gavage BALB/c female mice (6-8 week-old)
Pkd1v homozygous mice (mutation disrupting the G protein-coupled receptor proteolytic site cleavage site encoded in PKD1) were used. Pkd1v pups were treated with KPT-335 or vehicle by intraperitoneal injection biweekly starting at postnatal days 3 and 4 (P3 and P4). The pups received a weight-adjusted dosage of 5 mg/kg or a matching volume of vehicle. At 2 weeks of age, pups were euthanized and kidneys collected for assessment (kidney weight/body weight ratio) and staining [1]. |
| 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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| Additional Infomation |
Kpt 335 is being studied in the clinical trial NCT02431364 (Safety and tolerability trial of oral Verdinexor (Verdinexor) in healthy adults).
KPT-335 is a parallel inhibitor to KPT-330 (which is orally bioavailable and in phase 1 trials for cancers). The mechanism of action for XPO1 inhibition in ADPKD involves G0/G1 cell cycle arrest via downregulation of CDK4, mediated by nuclear confinement of C/EBPβ and subsequent upregulation of C/EBPα (though this mechanism was demonstrated with KPT-330 and KPT-251, not directly with KPT-335) [1]. |
| Molecular Formula |
C18H12F6N6O
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|---|---|---|
| Molecular Weight |
442.32
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| Exact Mass |
442.097
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| Elemental Analysis |
C, 48.88; H, 2.73; F, 25.77; N, 19.00; O, 3.62
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| CAS # |
1392136-43-4
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| Related CAS # |
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| PubChem CID |
71492799
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.577
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
620
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NNC1=NC=CC=C1)/C=C\N2N=C(C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)N=C2
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| InChi Key |
OPAKEJZFFCECPN-XQRVVYSFSA-N
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| InChi Code |
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-
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| Chemical Name |
(Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-N'-pyridin-2-ylprop-2-enehydrazide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2608 mL | 11.3040 mL | 22.6081 mL | |
| 5 mM | 0.4522 mL | 2.2608 mL | 4.5216 mL | |
| 10 mM | 0.2261 mL | 1.1304 mL | 2.2608 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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