Verdinexor (KPT-335) is an innovative, orally-administered selective inhibitor of nuclear export (SINE) that blocks the nuclear export protein Exportin 1 (XPO1/CRM1), showing efficacy against canine cancer cell lines[1]. KPT-335 effectively hinders cell proliferation, prevents colony formation, and triggers cell apoptosis at doses that are biologically significant. It also leads to a decrease in XPO1 protein levels alongside an increase in XPO1 mRNA levels. Additionally, treatment with KPT-335 elevates the expression and nuclear presence of the tumor suppressor proteins p53 and p21[3]. Prophylactic and therapeutic use of verdinexor offers protection to mice from influenza virus strains A/California/04/09 and A/Philippines/2/82-X79, lowering lung viral counts and inflammatory cytokine levels while showing minimal toxicity[1]. The inhibition of XPO1 by KPT-335 also curtails cyst growth in vivo in the Pkd1 mutant mouse model Pkd1v/v[4].
Verdinexor 细胞实验
Cell Line
Concentration
Treated Time
Description
References
BEAS-2B cells
1 μM
24 hours
To verify the inhibitory effect of KPT-335 on RSV A and B strains. Results showed that 1 μM KPT-335 inhibited replication of RSV A2, Long, and B1 strains.
J Virol. 2019 Feb 5;93(4):e01684-18.
A549 cells
1 μM
72 hours
To evaluate the inhibitory effect of KPT-335 on RSV replication. Results showed that 1 μM KPT-335 inhibited RSV A2 replication by ~50% without affecting cell viability.
J Virol. 2019 Feb 5;93(4):e01684-18.
KYSE510
20 μM
48 hours
To evaluate the inhibitory effect of Verdinexor on the proliferation of esophageal cancer cells
Int J Biol Sci. 2022 Jan 1;18(1):276-291.
KYSE180
20 μM
48 hours
To evaluate the inhibitory effect of Verdinexor on the proliferation of esophageal cancer cells
Int J Biol Sci. 2022 Jan 1;18(1):276-291.
KYSE450
20 μM
48 hours
To evaluate the inhibitory effect of Verdinexor on the proliferation of esophageal cancer cells
Int J Biol Sci. 2022 Jan 1;18(1):276-291.
KYSE30
20 μM
48 hours
To evaluate the inhibitory effect of Verdinexor on the proliferation of esophageal cancer cells
Int J Biol Sci. 2022 Jan 1;18(1):276-291.
Primary rat cortical neurons
10 μM
48 hours
To evaluate the protective effects of SINE compounds against TNF-α-induced neurotoxicity. Results showed that SINE compounds significantly increased cell viability and mitochondrial activity, with at least 50% and 100% increments in preservation of cell viability and cellular enzymatic activity, respectively, compared to non-treated neuronal cells (P<0.05).
CNS Neurosci Ther. 2016;22(4):306-315.
SH-SY5Y
0.3 µM
48 hours
To evaluate the inhibitory effect of Verdinexor on neuroblastoma cell proliferation. Results showed that Verdinexor significantly inhibited the proliferation of SH-SY5Y cells and induced apoptosis.
J Exp Clin Cancer Res. 2021 Aug 12;40(1):255.
SK-N-BE(2)
1.4 µM
48 hours
To evaluate the inhibitory effect of Verdinexor on neuroblastoma cell proliferation. Results showed that Verdinexor significantly inhibited the proliferation of SK-N-BE(2) cells and induced apoptosis.
J Exp Clin Cancer Res. 2021 Aug 12;40(1):255.
Bone marrow mononuclear cells (BMMC)
0.01 μM, 0.05 μM, 0.1 μM, 0.5 μM, 1 μM, 10 μM
24 hours-4 days
To evaluate the effect of Verdinexor on the survival of plasma cells in bone marrow and blood. Results showed that bone marrow-derived plasma cells were less sensitive to Verdinexor compared to those from blood.
Front Immunol. 2025 Jan 10;15:1499551.
293T cells
1 μM
6 hours
To evaluate the interference effect of Verdinexor on XPO1-NEP binding, results showed that Verdinexor reduced the binding of XPO1 to NEP
J Virol. 2014 Sep 1;88(17):10228-43.
MDCK cells
1 μM
2 hours
To evaluate the inhibitory effect of Verdinexor on influenza virus replication, results showed that Verdinexor effectively inhibited the replication of influenza virus A/California/04/09 (pH1N1)
J Virol. 2014 Sep 1;88(17):10228-43.
A549 cells
1 μM
2 hours
To evaluate the inhibitory effect of Verdinexor on influenza virus replication, results showed that Verdinexor effectively inhibited the replication of influenza virus A/WSN/33 (H1N1)
J Virol. 2014 Sep 1;88(17):10228-43.
VeroE6 cells
0.1 µM
4 days
To evaluate the inhibitory effect of Verdinexor on SARS-CoV-2 replication, results showed that 0.1 µM Verdinexor reduced viral replication by approximately 15%.
Front Cell Infect Microbiol. 2022 May 23;12:849017.
A549 cells
0.2μM
2 hours
To evaluate the inhibitory effect of Verdinexor on influenza virus replication
PLoS One. 2016 Nov 28;11(11):e0167221.
Verdinexor 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
Neuroblastoma xenograft model
Oral gavage
10 mg/kg
Three times per week for four weeks
To evaluate the antitumor effects of Verdinexor in vivo. Results showed that Verdinexor significantly inhibited tumor growth without causing obvious toxic effects.
J Exp Clin Cancer Res. 2021 Aug 12;40(1):255.
Nude mice
KYSE30 xenograft model
Intraperitoneal injection
5 mg/kg
24 days
To evaluate the inhibitory effect of Verdinexor on tumor growth of esophageal cancer in vivo
Int J Biol Sci. 2022 Jan 1;18(1):276-291.
BALB/c mice
Influenza virus infection model
Oral
10 or 20 mg/kg
Once daily for 3 days
To evaluate the antiviral effect of Verdinexor in vivo, results showed that Verdinexor reduced lung viral loads, decreased inflammatory responses, and improved survival rates
J Virol. 2014 Sep 1;88(17):10228-43.
Mice
Influenza virus infection model
Oral
20 mg/kg
Once on day 1 and day 3 post-infection
To evaluate the inhibitory effect of Verdinexor on influenza virus replication in vivo, results showed that Verdinexor significantly reduced virus shedding and pulmonary inflammatory response
PLoS One. 2016 Nov 28;11(11):e0167221.
Verdinexor 动物研究
Dose
Mice[3]: min = 10 mg/kg (p.o.), max = 50 mg/kg (p.o.); 5 mg/kg(i.v.)
搜索
