2. Membrane Transporter/Ion Channel
  3. CRM1
  4. Verdinexor

Verdinexor(KPT-335) is a novel, orally bioavailable selective inhibitor of nuclear export (SINE), inhibits nuclear export protein Exportin 1(XPO1/CRM1) against canine tumor cell lines; also reduce influenza virus replication in vitro and in vivo.

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Verdinexor Chemical Structure

Verdinexor Chemical Structure

CAS No. : 1392136-43-4

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
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Solid
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10 mg USD 240 In-stock
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Based on 2 publication(s) in Google Scholar

Verdinexor Related Antibodies

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  • Biological Activity

  • Purity & Documentation

  • References

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Description

Verdinexor(KPT-335) is a novel, orally bioavailable selective inhibitor of nuclear export (SINE), inhibits nuclear export protein Exportin 1(XPO1/CRM1) against canine tumor cell lines; also reduce influenza virus replication in vitro and in vivo. IC50 value: Target: SINE; XPO1/CRM1 in vitro: potently and selectively inhibit vRNP export and effectively inhibited the replication of various influenza virus A and B strains in vitro, including pandemic H1N1 virus, highly pathogenic H5N1 avian influenza virus, and the recently emerged H7N9 strain [1]. KPT-335 inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Lastly, KPT-335 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 [3]. in vivo: Prophylactic and therapeutic administration of verdinexor protected mice against disease pathology following a challenge with influenza virus A/California/04/09 or A/Philippines/2/82-X79, as well as reduced lung viral loads and proinflammatory cytokine expression, while having minimal toxicity [1]. A dose expansion study was performed in 6 dogs with NHL given 1.5 mg/kg KPT-335 Monday/Wednesday/Friday; CB was observed in 4/6 dogs with a median TTP for responders of 83 days (range 35-354 days). Toxicities were primarily gastrointestinal consisting of anorexia, weight loss, vomiting and diarrhea and were manageable with supportive care, dose modulation and administration of low dose prednisone; hepatotoxicity, anorexia and weight loss were the dose limiting toxicities [2]. Inhibition of XPO1 with KPT-335 attenuated cyst growth in vivo in the PKD1 mutant mouse model Pkd1v/v [4].

Cellular Effect
Cell Line Type Value Description References
MDCK CC50
31.77 μM
Compound: Verdinexor
Cytotoxicity against MDCK cells assessed as cell death after 72 hrs by MTT assay
Cytotoxicity against MDCK cells assessed as cell death after 72 hrs by MTT assay
[PMID: 30753063]
SH-SY5Y IC50
0.3 μM
Compound: 12; KPT-335
Antiproliferative activity against human SH-SY5Y cells by CCK-8 assay
Antiproliferative activity against human SH-SY5Y cells by CCK-8 assay
[PMID: 34669417]
SK-N-BE(2) IC50
1.4 μM
Compound: 12; KPT-335
Antiproliferative activity against human SK-N-BE(2) cells by CCK-8 assay
Antiproliferative activity against human SK-N-BE(2) cells by CCK-8 assay
[PMID: 34669417]
Molecular Weight

442.32

Formula

C18H12F6N6O
CAS No.
Appearance

Solid

Color

Light yellow to yellow

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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : ≥ 100 mg/mL (226.08 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
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Concentration
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Volume
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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

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Volume (start)

V1

=
Concentration (final)

C2

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Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (5.65 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (5.65 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, PEG300/PEG400, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.2608 mL 11.3040 mL 22.6081 mL 56.5202 mL
5 mM 0.4522 mL 2.2608 mL 4.5216 mL 11.3040 mL
10 mM 0.2261 mL 1.1304 mL 2.2608 mL 5.6520 mL
15 mM 0.1507 mL 0.7536 mL 1.5072 mL 3.7680 mL
20 mM 0.1130 mL 0.5652 mL 1.1304 mL 2.8260 mL
25 mM 0.0904 mL 0.4522 mL 0.9043 mL 2.2608 mL
30 mM 0.0754 mL 0.3768 mL 0.7536 mL 1.8840 mL
40 mM 0.0565 mL 0.2826 mL 0.5652 mL 1.4130 mL
50 mM 0.0452 mL 0.2261 mL 0.4522 mL 1.1304 mL
60 mM 0.0377 mL 0.1884 mL 0.3768 mL 0.9420 mL
80 mM 0.0283 mL 0.1413 mL 0.2826 mL 0.7065 mL
100 mM 0.0226 mL 0.1130 mL 0.2261 mL 0.5652 mL
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Verdinexor Related Classifications

Keywords:

Verdinexor1392136-43-4KPT-335KPT335KPT 335CRM1Chromosomal Maintenance 1Exportin 1XPO1Inhibitorinhibitorinhibit

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