Eltanexor, also known as KPT-8602, is a second-generation, orally administered inhibitor that is highly selective for exportin-1 (XPO1), exhibiting strong anti-leukemic properties. It effectively blocks XPO1-dependent nuclear export with an EC50 of 60.9 nM by directly interacting with XPO1.Eltanexor, administered at concentrations between 2 and 6 nM for a duration of 72 hours, diminishes cell viability in leukemia cell lines, with EC50 values spanning from 25 to 145 nM. Also, it triggers apoptosis in leukemia cell lines[1].
Eltanexor 细胞实验
Cell Line
Concentration
Treated Time
Description
References
U266-LR6
300 nM
20 hours
XPO1 inhibitors significantly increased sensitivity to MEL
Cancer Res. 2020 Dec 1;80(23):5344-5354.
8226-LR5
300 nM
20 hours
XPO1 inhibitors significantly increased sensitivity to MEL
Cancer Res. 2020 Dec 1;80(23):5344-5354.
8226
300 nM
20 hours
SEL or KOS-2464 increased apoptosis in a dose-dependent manner
Evaluate the therapeutic efficacy of Eltanexor in GBM stem-like cells, IC50 values below 200 nM, significantly reducing cell viability and increasing apoptosis rates
Biomedicines. 2022 Aug 31;10(9):2145.
IMS-M2
50 nM
11 days
Inhibited growth of NPM1-mutated cells and induced differentiation
Blood Adv. 2022 Nov 22;6(22):5938-5949.
U251 GB cells
100 nM
12 hours
Evaluate the effect of Eltanexor on XPO1 gene expression in U251 cells, showing significant upregulation of XPO1 mRNA
(Eltanexor, Venetoclax, and A1210477) Inhibiting XPO1, Bcl-2, and Mcl-1. Cells.
U87 GB cells
100 nM
12 hours
Evaluate the effect of Eltanexor on XPO1 gene expression in U87 cells, showing significant upregulation of XPO1 mRNA
(Eltanexor, Venetoclax, and A1210477) Inhibiting XPO1, Bcl-2, and Mcl-1. Cells.
RPMI-8402
50 nM
14 days
To test the synergistic effect of MRK-560 and KPT-8602, results showed that all NOTCH1-dependent cell lines were sensitive to KPT-8602, and the combination significantly inhibited leukemia proliferation and/or induced cell death
J Hematol Oncol. 2021 Jun 24;14(1):97.
ALL-SIL
50 nM
14 days
To test the synergistic effect of MRK-560 and KPT-8602, results showed that all NOTCH1-dependent cell lines were sensitive to KPT-8602, and the combination significantly inhibited leukemia proliferation and/or induced cell death
J Hematol Oncol. 2021 Jun 24;14(1):97.
DND-41
50 nM
14 days
To test the synergistic effect of MRK-560 and KPT-8602, results showed that all NOTCH1-dependent cell lines were sensitive to KPT-8602, and the combination significantly inhibited leukemia proliferation and/or induced cell death
J Hematol Oncol. 2021 Jun 24;14(1):97.
NALM6
1 µM
16 hours
To assess the sensitivity of SF3B1 mutant cells to XPO1 inhibition, results showed increased sensitivity of SF3B1 mutant cells to eltanexor
Leukemia. 2024 Sep;38(9):1894-1905.
U266
300 nM
20 hours
SEL or ELT combined with MEL significantly increased apoptosis compared to MEL alone
Cancer Res. 2020 Dec 1;80(23):5344-5354.
H929
300 nM
20 hours
SEL or ELT combined with MEL significantly increased apoptosis compared to MEL alone
Cancer Res. 2020 Dec 1;80(23):5344-5354.
GSCs (glioblastoma stem-like cells)
10 nM
48 hours
Evaluate the effect of Eltanexor on XPO1 gene expression in GSCs, showing significant upregulation of XPO1 mRNA
(Eltanexor, Venetoclax, and A1210477) Inhibiting XPO1, Bcl-2, and Mcl-1. Cells.
HEK293
0.01 µM and 0.1 µM
48 hours
Evaluate the inhibitory effect of Eltanexor on HEK293 cell proliferation, showing increased sensitivity of E571K mutant cells to KPT-330 (Selinexor) at 0.01 μM and 0.1 μM doses
J Hematol Oncol. 2021 Jan 15;14(1):17.
K562
1 µM
48 hours
To validate the sensitivity of DDX19A knockdown to XPO1 inhibition, results showed that DDX19A knockdown increased sensitivity to eltanexor
Leukemia. 2024 Sep;38(9):1894-1905.
Bone marrow-derived macrophages (BMMs)
0, 25, 50, 75, 100 nM
5 days
To evaluate the inhibitory effect of Eltanexor on RANKL-induced osteoclast formation. Results showed that Eltanexor inhibited osteoclast formation in a dose-dependent manner.
Front Pharmacol. 2022 Aug 30;13:896108.
U251
1 nM to 10 µM
5 days
Evaluate the therapeutic efficacy of Eltanexor in GBM cell lines, IC50 values below 100 nM, significantly reducing cell viability and increasing apoptosis rates
Biomedicines. 2022 Aug 31;10(9):2145.
U87
1 nM to 10 µM
5 days
Evaluate the therapeutic efficacy of Eltanexor in GBM cell lines, IC50 values below 100 nM, significantly reducing cell viability and increasing apoptosis rates
Biomedicines. 2022 Aug 31;10(9):2145.
PDX2 and PDX3
50 nM
7 to 9 days
Induced increased CD11b expression in NPM1-mutated primary AML samples
Blood Adv. 2022 Nov 22;6(22):5938-5949.
SNU-16
150 nM
72 hours
Inhibited cell proliferation, induced apoptosis, and halted cell cycle progression at the G1/S phase
Int J Mol Sci. 2019 Sep 28;20(19):4826.
SNU-1
150 nM
72 hours
Inhibited cell proliferation, induced apoptosis, and halted cell cycle progression at the G1/S phase
Int J Mol Sci. 2019 Sep 28;20(19):4826.
Primary MF CD34+ cells
50-100 nM
72 hours
Evaluate the effect of KPT-8602 on primary MF CD34+ cell viability and apoptosis, showing selective suppression of MF cell growth and induction of apoptosis
Clin Cancer Res. 2019 Apr 1;25(7):2323-2335.
HEL-R cells
100 nM
72 hours
Evaluate the effect of KPT-8602 on JAK inhibitor-resistant HEL-R cell viability, showing IC50 ~100 nM
Clin Cancer Res. 2019 Apr 1;25(7):2323-2335.
SET-2 cells
100 nM
72 hours
Evaluate the effect of KPT-8602 on SET-2 cell viability, showing IC50 ~100 nM
Clin Cancer Res. 2019 Apr 1;25(7):2323-2335.
HEL cells
100 nM
72 hours
Evaluate the effect of KPT-8602 on HEL cell viability, showing IC50 ~100 nM
Clin Cancer Res. 2019 Apr 1;25(7):2323-2335.
OCI-AML3
50 nM
72 hours
Induced differentiation of NPM1-mutated AML cells, characterized by HOX/MEIS downregulation and increased CD11b expression
Blood Adv. 2022 Nov 22;6(22):5938-5949.
NB4 cells
264 nM (GI50)
72 hours
To evaluate the growth inhibitory effect of Eltanexor on NB4 cells, the results showed a GI50 of 264 nM.
Blood Adv. 2020 Feb 11;4(3):586-598.
U-937 cells
131 nM (GI50)
72 hours
To evaluate the growth inhibitory effect of Eltanexor on U-937 cells, the results showed a GI50 of 131 nM.
Blood Adv. 2020 Feb 11;4(3):586-598.
MOLM-16 cells
59 nM (GI50)
72 hours
To evaluate the growth inhibitory effect of Eltanexor on MOLM-16 cells, the results showed a GI50 of 59 nM.
Blood Adv. 2020 Feb 11;4(3):586-598.
K-562 cells
104 nM (GI50)
72 hours
To evaluate the growth inhibitory effect of Eltanexor on K-562 cells, the results showed a GI50 of 104 nM.
Blood Adv. 2020 Feb 11;4(3):586-598.
MOLM-13 cells
32 nM (GI50)
72 hours
To evaluate the growth inhibitory effect of Eltanexor on MOLM-13 cells, the results showed a GI50 of 32 nM.
Blood Adv. 2020 Feb 11;4(3):586-598.
MV-4-11 cells
22 nM (GI50)
72 hours
To evaluate the growth inhibitory effect of Eltanexor on MV-4-11 cells, the results showed a GI50 of 22 nM.
Blood Adv. 2020 Feb 11;4(3):586-598.
Human foreskin fibroblasts (HFFs)
0.03762 µM (IC50)
72 hours
To evaluate the inhibitory effect of Eltanexor on HCMV replication. Results showed that Eltanexor inhibits HCMV replication in a dose-dependent manner with an IC50 of 0.03762 μM.
Front Microbiol. 2021 May 3;12:675112.
Eltanexor 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J female mice
Ovariectomized (OVX) osteoporosis model
Intraperitoneal injection
0.075 mg/kg and 0.15 mg/kg
Every 2 days, continuous treatment
To evaluate the protective effect of Eltanexor on ovariectomy-induced osteoporosis. Results showed that Eltanexor significantly reduced bone loss and increased trabecular bone number.
Front Pharmacol. 2022 Aug 30;13:896108.
Mice
Healthy mouse brain slice culture
In vitro culture
1 µM
48 hours
Evaluate the toxicity of Eltanexor combined with chemotherapy drugs on healthy brain tissue, showing no significant cell death
(Eltanexor, Venetoclax, and A1210477) Inhibiting XPO1, Bcl-2, and Mcl-1. Cells.
ICR-nude female mice
SNU-1 xenograft model
Oral
10 mg/kg
Every other day for three weeks
Significantly enhanced tumor inhibition in combination with nab-paclitaxel
Int J Mol Sci. 2019 Sep 28;20(19):4826.
Mice
Sf3b1 K700E conditional knock-in mice
Oral gavage
10 mg/kg
5 days per week for two weeks
To evaluate the effect of combination therapy of eltanexor with BCL inhibitors, results showed that the combination of eltanexor and venetoclax significantly reduced Sf3b1 mutant cells
Leukemia. 2024 Sep;38(9):1894-1905.
NOD/SCID-γ mice
Human U266 and U266-LR6 MM tumor models
Oral gavage
10 mg/kg
Twice weekly, continuous treatment
SEL or ELT combined with MEL significantly reduced tumor growth and improved survival
Cancer Res. 2020 Dec 1;80(23):5344-5354.
Balb/c mice
JAK2V617F-driven MPN model
Oral
10 mg/kg
Twice weekly for 28 days
Evaluate the effect of KPT-330 alone or in combination with ruxolitinib on the MPN model, showing combination treatment significantly reduced white blood cells, spleen GFP+ cells and spleen weight, and partially restored splenic architecture
Clin Cancer Res. 2019 Apr 1;25(7):2323-2335.
NSG mice
PDX2 and PDX3 models
Oral gavage
10 mg/kg
5 days per week for 4 weeks
Significantly reduced leukemic burden and prolonged survival
Blood Adv. 2022 Nov 22;6(22):5938-5949.
Mice
Wilms tumor PDX models
Oral gavage
15 mg/kg
Five times per week for 4 weeks
Evaluate the anti-tumor activity of eltanexor in Wilms tumor PDX models, showing similar anti-tumor effects as selinexor
Med. 2022 Nov 11;3(11):774-791.e7.
Zebrafish
Tet2-mutant zebrafish embryos
Embryo water immersion
250 nM
From 1 dpf to 5 dpf
Evaluate the selective killing effect of Eltanexor on tet2-mutant zebrafish embryo HSPCs, results showed Eltanexor selectively killed tet2-mutant HSPCs.
Br J Haematol. 2023 May;201(3):489-501
Mice
T-ALL patient-derived xenograft model
Oral
5 mg/kg
Once daily for 14 days
To test the in vivo synergistic effect of MRK-560 and KPT-8602, results showed that combination treatment significantly reduced leukemic burden and prolonged survival
J Hematol Oncol. 2021 Jun 24;14(1):97.
NSGS mice
MV-4-11 AML xenograft model
Oral gavage
7.5 mg/kg
5 days per week for 3 weeks
To evaluate the anti-leukemic effects of Eltanexor in the MV-4-11 AML xenograft model, the results showed that combination treatment significantly reduced leukemia burden in peripheral blood, bone marrow, and spleen.
Blood Adv. 2020 Feb 11;4(3):586-598.
Eltanexor 动物研究
Animal study
Administered through oral gavage at a dose of 15 mg/kg daily for 12 days, KPT-8602 exhibits strong activity against lymphoblastic leukemia[1].
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