Journal: Cellular and Molecular Life Sciences

Article Title: Novel carfilzomib-based combinations as potential therapeutic strategies for liposarcomas

doi: 10.1007/s00018-020-03620-w

Figure Lengend Snippet: Selinexor potentiates effects of carfilzomib in LPS. a Viability assays of MLS402 cells treated with either carfilzomib, selinexor or combinations of both ( n = 2 experiments performed in duplicate, values indicate mean ± SD). Right panels: heatmaps of HSA ( H ighest S ingle A gent) synergy and antagonism scores generated using Combenefit Software . A score < −10 shows antagonism, a score between −10 and 10 shows the additive effect and a score > 10 depicts synergy between the drugs. Only scores ≥ 10 are depicted. b Representative Colony formation assay of MLS402 cells treated with combinations of carfilzomib and selinexor. Middle panel represents relative absorbance values ± SD. Right panel depicts the HSA scores. c Schematic of SILAC labeling of LPS cells in either ‘heavy’ or ‘light’ medium before drug treatment for 24 h, and subsequent nuclear proteins extraction and processing for LC–MS/MS analysis. d Two-dimensional SILAC ratio plots showing quantified proteins by mass spectrometry analysis in MLS402 cells treated with either selinexor (60 nM), carfilzomib (15 nM) or their combination. Proteins in the top left quadrant of each plot are accumulated after drug treatment (log2 fold change > 1), while those on the bottom right are depleted (log2 fold change < −1). Smaller panels are enlarged view of the annotated quadrants ( a – d ). Accumulated (in red) or depleted (in green) proteins are annotated. Proteins in blue are those differentially expressed only in the drug combination treatment. e Quantification of signal intensities of two phosphorylated kinases (PRAS40 and WNK1) from phospho-kinase arrays of MLS402 treated with either DMSO, carfilzomib (15 nM), selinexor (60 nM) or a combination of both. Left panels are a magnification of highlighted spots in (Supplementary Figure S2C). Right panels show the mean ± SD of signal intensities calculated using Image Studio Lite software. f , h qRT-PCR analysis of relative expression of PRAS40 or WNK1 transcripts in MLS402 cells transduced with either shControl or shPRAS40 ( f ) or shWNK1 ( h ). Values represent mean ± SEM of three experiments. g , i Growth curves of MLS402 shControl and shPRAS40 or shWNK1 cells. Values represent mean ± SEM of at least two experiments performed in triplicate. (ns = not significant, ** p < 0.01, as determined by two-tailed Mann–Whitney test)

Article Snippet: MLS402 cells were treated with either carfilzomib, selinexor or combination of both for 24 h. 600 μg of protein extracts were used to perform kinase phosphorylation profiling using Proteome Profiler Human Phospho-Kinase Array Kit (R&D System, ARY003B) according to the manual’s instructions.

Techniques: Generated, Software, Colony Assay, Multiplex sample analysis, Labeling, Extraction, Liquid Chromatography with Mass Spectroscopy, Mass Spectrometry, Quantitative RT-PCR, Expressing, Transduction, Two Tailed Test, MANN-WHITNEY

Journal: Cell Reports Methods

Article Title: Phenotypic deconvolution in heterogeneous cancer cell populations using drug-screening data

doi: 10.1016/j.crmeth.2023.100417

Figure Lengend Snippet: Phenotypic deconvolution of drug screens from MM patient samples (A) Illustration of the experimental protocol described in STAR Methods,26 created using smart.servier.com and biorender.com. (B–G) Deconvolution results for 5 MM samples, each exposed to 4 out of 6 drugs: (B) dexamethasone, (C) selinexor, (D) melflufen, (E) venetoclax, (F) ixazomib, and (G) thalidomide. In (B)–(G) separately, each row corresponds to a patient sample. On the left, the estimated mixture percentages are shown. On the right, the grid of vertical lines corresponds to drug concentrations. The estimated GR50 region is shown by a colored box, and the point estimate of the GR50 is marked with the white circle. If the inferred GR50 value of a population is above the highest observed concentration, the estimated GR50 is instead marked by an arrow pointing toward the right from the highest observed concentration.

Article Snippet: Selinexor (CRM1 inhibitor) , BOC Sciences , 1,393,477-72-9.

Techniques: Concentration Assay

Journal: Cell Reports Methods

Article Title: Phenotypic deconvolution in heterogeneous cancer cell populations using drug-screening data

doi: 10.1016/j.crmeth.2023.100417

Figure Lengend Snippet: Key resources table

Article Snippet: Selinexor (CRM1 inhibitor) , BOC Sciences , 1,393,477-72-9.

Techniques: Mutagenesis, Derivative Assay, Recombinant, Software, High Content Screening

Journal: Neoplasia (New York, N.Y.)

Article Title: Overcoming Tyrosine Kinase Inhibitor Resistance in Transformed Cell Harboring SEPT9-ABL1 Chimeric Fusion Protein

doi: 10.1016/j.neo.2019.06.001

Figure Lengend Snippet: The effect of the CRM1 inhibitor KPT-330 on SEPT9-ABL1 in vitro . (A) The IC 50 and the dose-response curve of the CRM1 inhibitor KPT-330 in 32D and BaF3 cells expressing BCR-ABL1 or SEPT9-ABL1. The cells were analyzed at 48 hours after starting culture with various concentrations of KPT-330. These experiments were repeated five times, and the median values of IC 50 are shown. Additionally, the representative dose-response curves are shown. (B). The CRM1 expression in 32D cells expressing BCR-ABL1 and SEPT9-ABL1. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or the combination of imatinib and KPT-330 for 24 hours, the protein expression was evaluated by a Western blot analysis. These experiments were performed three times. (C) The cellular TRP53 distribution in 32D/BCR-ABL1 and 32D/SEPT9-ABL1 treated with KPT-330. After culturewithout treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or combination of imatinib and KPT-330 for 4 hours, the cells were fractionated and evaluated by a Western blot analysis. These experiments were performed three times, and the representative images are shown. (D) The cellular distribution of NFKB1A in 32D cells expressing BCR-ABL1 and SEPT9-ABL1. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or the combination of imatinib and KPT-330 for 24 hours, the cells were fractionated and evaluated by a Western blot analysis. These experiments were performed three times. (E) The PP2A phosphorylation and SET expression in 32D/BCR-ABL1 and 32D/SEPT9-ABL1 treated with KPT-330 and/or imatinib. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 10 μM, or combination of imatinib and KPT-330 for 24 hours, the protein expressions were evaluated by a Western blot analysis. These experiments were performed three times, and the representative images are shown. The arrows and asterisks indicate the specific and nonspecific bands, respectively. The bars below the images indicated the ratio of p-PP2A/ACTB, PP2A/ACTB, and SET/ACTB in comparison with those from untreated controls in 32D/BCR-ABL1 and 32D/SEPT9-ABL1, whichwere calculated from all the analyzed data. * indicates a P value <.05. (F) The cellular distribution of PP2A and SET in 32D cells expressing BCR-ABL1 and SEPT9-ABL1. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or the combination of imatinib and KPT-330 for 24 hours, the cells were fractionated and evaluated by a Western blot analysis. These experiments were performed three times. The arrows and asterisks indicate the specific and nonspecific bands, respectively. (G) The TIAM1 expression in 32D/BCR-ABL1 and 32D/SEPT9-ABL1 treated with KPT-330 and/or imatinib. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or combination of imatinib and KPT-330 for 24 hours, the protein expression was evaluated by a Western blot analysis. (H, I) The frequency of Annexin V and PI double-positive cells in 32D cells (D) and BaF3 cells (E) harboring BCR-ABL1 or SEPT9-ABL1 that were cultured without treatment or with imatinib 1 μM, KPT-330 1 μM, or the combination of imatinib 1 μM and KPT-330 1 μM. The analyses were performed 24 hours after treatment using a flow cytometry. These experiments were performed five times. * indicates a P value <.05.

Article Snippet: The CRM1 antagonist, termed a selective inhibitor of nuclear export (SINE), KPT-330 (Selleck Chemicals, Houston, TX) and imatinib (Santa Cruz Biotechnology, Dallas, TX) were dissolved in DMSO at 50 mM for KPT-330 and 100 mM for imatinib.

Techniques: In Vitro, Expressing, Western Blot, Cell Culture, Flow Cytometry

Journal: Neoplasia (New York, N.Y.)

Article Title: Overcoming Tyrosine Kinase Inhibitor Resistance in Transformed Cell Harboring SEPT9-ABL1 Chimeric Fusion Protein

doi: 10.1016/j.neo.2019.06.001

Figure Lengend Snippet: The effect of the CRM1 inhibitor on SEPT9-ABL1 in vivo . The changes in the tumor volume in the subcutaneous tumor model. BALB/c mice transplanted with 5 × 10 6 BaF3/SEPT9-ABL1 cells subcutaneously were treated with imatinib 20 mg/kg daily ( n = 5), KPT-330 5mg/kg 3 times/week ( n 6), or imatinib 20mg/kg daily and KPT-330 5mg/kg 3 times/week ( n = 5) from 10 days after transplantation. The calculated volume of the subcutaneous tumors is indicated at the vertical axis. * indicates a P value <.05. (B) The pathohistology of the involved organs in leukemic mice with BaF3/SEPT9-ABL1 cells. The histological sections stained with hematoxylin and eosin are shown. BaF3/SEPT9-ABL1 cells infiltrated diffusely throughout the bone marrow, predominantly in the red pulp of spleen, and the lobules as well as around the vessels and Glisson's sheath in the liver. * indicates tumor cells. The magnification ratio was showed at 20× in the upper figures and at 100× in the lower figure. The bars indicate 200 μm in the upper figures and 50 μm in the lower figures. (C) The Kaplan-Meier survival curves of the intraperitoneal tumor model. BALB/c mice transplanted with 2 × 10 6 BaF3/SEPT9-ABL1 cells intraperitoneally were treated with vehicle ( n = 3), imatinib 20 mg/kg daily ( n = 7), KPT-330 50 mg/kg 3 times/week ( n = 8), or imatinib 20 mg/kg daily and KPT-330 50 mg/kg 3 times/week ( n = 12) from the day after transplantation. * indicates a P value <.05 (imatinib and KPT-330 vs. imatinib), and **indicates a P value <.05 (imatinib and KPT-330 vs. KPT-330). (D) The Kaplan-Meier survival curves of the intraperitoneal tumor model. BALB/c mice transplanted with 2 10 6 32D/SEPT9-ABL1 cells intraperitoneally were treated with vehicle ( n = 3), imatinib 20 mg/kg daily ( n = 7), KPT-330 50 mg/kg 3 times/week ( n = 7), or imatinib 20 mg/kg daily and KPT-330 50 mg/kg 3 times/week ( n = 8) from the day after transplantation. * indicates a P value <.05 (imatinib and KPT-330 vs. imatinib), **indicates a P value <.05 (imatinib and KPT-330 vs. KPT-330), and ***indicates a P value <.05 (imatinib vs. KPT-330).

Article Snippet: The CRM1 antagonist, termed a selective inhibitor of nuclear export (SINE), KPT-330 (Selleck Chemicals, Houston, TX) and imatinib (Santa Cruz Biotechnology, Dallas, TX) were dissolved in DMSO at 50 mM for KPT-330 and 100 mM for imatinib.

Techniques: In Vivo, Transplantation Assay, Staining

Journal: Translational Oncology

Article Title: The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1/Raf/MEK pathway-mediated MYC downregulation

doi: 10.1016/j.tranon.2025.102399

Figure Lengend Snippet: Low-dose triptolide (LD TPL) and selinexor are synergistic in decreasing cell viability and promoting cell apoptosis in MLL-r AML cells. (A-B) Analysis of cell viability of Molm13 (A) and MV4–11 (B) cells treated with a series of TPL and selinexor alone or in combination for 24 and 48 hour. (C-D) Analysis of the combination index (CI) of TPL combined with selinexor in Molm13 (C) and MV4–11 (D) cells. CompuSyn software was adopted to calculate the CI based on the Chou-Talalay method. CI < 1 indicates a synergistic effect; CI =1, an additive effect; and CI <1, an antagonistic effect. (E-F) LD TPL combined with selinexor significantly induced cell apoptosis in Molm13 (E) and MV4–11 (F) cells when compared with LD TPL and selinexor monotherapies, independent of treatment durations. (G-H) TPL combined with selinexor showed synergistic effects on Molm13 (G) and MV4–11 (H) cells, manifested by CI < 1. (I) Assessment of the therapeutic interaction of LD TPL coupled with selinexor in primary AML cells. ns represents not significant. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Article Snippet: TPL (formula: C20H24O6, MW: 360.40) and selinexor were purchased from Targetmol (Boston, Massachusetts, USA) and AbbVie (Chicago, IL, USA), respectively.

Techniques: Software

Journal: Translational Oncology

Article Title: The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1/Raf/MEK pathway-mediated MYC downregulation

doi: 10.1016/j.tranon.2025.102399

Figure Lengend Snippet: The cooperative effects of LD TPL and selinexor on the induction of mitochondrial membrane depolarization, elevation of ROS levels and dysregulation of BCL2 family proteins. (A-B) Analysis of mitochondrial membrane potential (MMP) of Molm13 cells exposed to LD TPLand selinexor alone or in combined treatment for 24 (A) or 48 (B) hours. (C-D) Measurement of the MMP level of MV4–11 cells treated with LD TPLand selinexor alone or in combination for 24 (C) or 48 (D) hours. (E-F) Detection of the ROS level of Molm13 (E) and MV4–11 (F) cells treated with LD TPLand selinexor alone or in combination for 24 hours. (G-H) Western blot probed the expression levels of the indicated proteins in MV4–11 (G) and Molm13 (H) cells treated with TPL (7.5 nM) and selinexor (1000 nM) alone or incombination for 48 hours. (I-J) Detection of the indicated BCL2 family proteins in MV4–11 (I) and Molm13 (J) cells treated with LD TPL and selinexor alone or in combination for 6, 12, and 24 hours. ns represents not significant. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Article Snippet: TPL (formula: C20H24O6, MW: 360.40) and selinexor were purchased from Targetmol (Boston, Massachusetts, USA) and AbbVie (Chicago, IL, USA), respectively.

Techniques: Membrane, Western Blot, Expressing

Journal: Translational Oncology

Article Title: The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1/Raf/MEK pathway-mediated MYC downregulation

doi: 10.1016/j.tranon.2025.102399

Figure Lengend Snippet: Transcriptomic analysis reveals the molecular mechanism by which LD TPL combined with selinexor synergistically kill MLL-r AML cells. (A-C) Volcano plot analysis of the significant expression differences of TPL monotherapy (A) , selinexor monotherapy (B) , or the combined regimen (C) versus the control group, respectively. (D) The venn diagraph showed the number of genes and their relationship that were differentially expressed (log2FC ≥ 1, Q value ≤ 0.001) after treatment with TPL and selinexor alone or in combination, compared to the untreated group. (E-G) The KEEG analysis revealed the annotations of the most enriched pathways of differentially expressing genes after TPL, selinexor and the combined treatment in comparison to the untreated control.

Article Snippet: TPL (formula: C20H24O6, MW: 360.40) and selinexor were purchased from Targetmol (Boston, Massachusetts, USA) and AbbVie (Chicago, IL, USA), respectively.

Techniques: Expressing, Control, Comparison

Journal: Translational Oncology

Article Title: The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1/Raf/MEK pathway-mediated MYC downregulation

doi: 10.1016/j.tranon.2025.102399

Figure Lengend Snippet: Rap1/Raf/MEK/ERK pathway inactivation and DNA damage induction contribute to the synergy of LD TPL and selinexor in MLL-r AML cells. Measurement of the expression of proteins involved in the Rap1/Raf/MEK/ERK pathway and DNA damage response in MV4–11 (A) and Molm13 (B) cells, which were treated with TPL (7.5 nM) and selinexor (1000 nM) alone or in combination for 24 hours.

Article Snippet: TPL (formula: C20H24O6, MW: 360.40) and selinexor were purchased from Targetmol (Boston, Massachusetts, USA) and AbbVie (Chicago, IL, USA), respectively.

Techniques: Expressing

Journal: Translational Oncology

Article Title: The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1/Raf/MEK pathway-mediated MYC downregulation

doi: 10.1016/j.tranon.2025.102399

Figure Lengend Snippet: The combined regimen of TPL with selinexor is effective in MLL-r AML xenograft models. (A) Evaluation of the synergistic antileukemic activity of TPL coupled with selinexor in MLL-r AML xenograft models, evidenced by lower GFP/luciferase levels in the combined group than the control group and each single drug groups. (B-C) In contrast to the untreated and monotherapy groups, the combined regimen significantly decreased the leukemia burdern in bone marrow (BM, B ) and Brain (C). (D) Neither each single drug alone nor the combined treatment affected the body weight of the MLL-r AML xenograft models. (E) HE staining analysis of leukemia burden in spleen, liver and brain in the four distinct treatment groups. (F) Immunohistochemistry (IHC) analysis of the expression of Cleaved-caspase 3, PARP, and c-MYC in spleen, bone marrow and liver.

Article Snippet: TPL (formula: C20H24O6, MW: 360.40) and selinexor were purchased from Targetmol (Boston, Massachusetts, USA) and AbbVie (Chicago, IL, USA), respectively.

Techniques: Activity Assay, Luciferase, Control, Staining, Immunohistochemistry, Expressing

Journal: Translational Oncology

Article Title: The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1/Raf/MEK pathway-mediated MYC downregulation

doi: 10.1016/j.tranon.2025.102399

Figure Lengend Snippet: The synergistic antileukemia efficacy of TPL together with selinexor on a MLL-r AML patient-derived xenograft (PDX) mouse model. (A) The scheme of MLL-r AML PDX model treated with TPL and Selinexor alone or in combination for two weeks. (B-C) Spleen size (B) and weight (C) measurement of PDX models treated as (A). (D-F) Leukemia burden was detected in spleen (D) , BM (E) , and peripheral blood (F) in distinct treatment groups. (G) Kaplan-Meier analysis was performed to assess animal survival.

Article Snippet: TPL (formula: C20H24O6, MW: 360.40) and selinexor were purchased from Targetmol (Boston, Massachusetts, USA) and AbbVie (Chicago, IL, USA), respectively.

Techniques: Derivative Assay

Journal: Cancer Discovery

Article Title: Mutant NPM1 Hijacks Transcriptional Hubs to Maintain Pathogenic Gene Programs in Acute Myeloid Leukemia

doi: 10.1158/2159-8290.CD-22-0424

Figure Lengend Snippet: XPO1 nuclear export inhibition displaces NPM1c from chromatin. A, The binding profiles of NPM1c, XPO1, and H3K27ac at NPM1c binding genes in OCI-AML3 cells from −3 kb TSS to +3 kb transcriptional end site (TES). B, The peak overlap between NPM1c and XPO1 peaks (left) and genes with TSS peak (right) in OCI-AML3 NPM1c degron 2 cells. C, Coimmunoprecipitation (IP) of NPM1c and XPO1 in OCI-AML3 cells. D, Confocal immunofluorescence image of colocalization of NPM1ca-eGFP and XPO1 in NPM1ca-eGFP HOXB8 cells. DAPI was used to stain the DNA of the nucleus. Scale bar = 10 μm. E and F, The NPM1c ( E ) and XPO1 ( F ) binding profiles in 6,312 NPM1c binding genes with 500 nmol/L dTAG-13 and 25 nmol/L selinexor treatment for 24 hours in OCI-AML3 NPM1c degron 2 cells (−5 kb TSS to + 5 kb TES). G, Integrative Genomics Viewer view of NPM1c and XPO1 enrichment and distribution at the HOXA cluster, MEIS1, and the HOXB cluster in OCI-AML3 NPM1c degron 2 cells with 500 nmol/L dTAG-13 and 25 nmol/L selinexor treatment. H, Venn diagram showing the overlap between the downregulated genes in dTAG-13 and selinexor treatment. The representative overlapping genes are listed. P value is calculated by the Fisher exact test for 2 × 2 contingency table. I, The volcano plot shows the differential transcription genes on the gene body Bru-seq reads with 12 hours of 25 nmol/L selinexor treatment in OCI-AML3 NPM1c degron 2 cells. The horizontal dashed line indicates the cutoff for P = 0.01. The vertical dashed line indicates the 1.5-fold cutoff for fold change in gene expression. J, The Bru-seq reads of nascent transcription at the MEIS1 (left) and LHX2 (right) locus. RPKM, reads per kilobase million. K, Two color confocal fluorescence images of a U2OS LacO array cell cotransfected with EYFP-LacI with mCherry-XPO1 (top), and images of cells cotransfected with EYFP-NPM1c-LacI and mCherry-XPO1 (bottom). The LacO array locus is circled, and magnified LacO array locus images are shown at the lower left part of the image. The nucleus (nuc) is annotated in the bottom images. L, Enrichment of mCherry signal quantification at the LacO array locus in the cells transfected in K . Mean ± SD is shown. P value is calculated by the Student t test.

Article Snippet: Total RNA from OCI-AML3 cells treated with DMSO, dTAG-13, and selinexor (ApexBio, B1464) with specific doses and time was isolated using the Qiagen RNeasy RNA isolation kit (micro).

Techniques: Inhibition, Binding Assay, Immunofluorescence, Staining, Expressing, Fluorescence, Transfection

Journal: Journal of Korean Medical Science

Article Title: Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval

doi: 10.3346/jkms.2024.39.e134

Figure Lengend Snippet: Other medications for COVID-19 (N = 19)

Article Snippet: Xpovio (selinexor) , Karyopharm Therapeutics , USA , Antiviral activity & Anti-inflammation , p53 inhibitor & inhibition of pro-inflammatory cytokine & activating Nrf2, PPAR-γ , 2 , NCT04349098 (Completed) , January 20, 2023 , https://www.karyopharm.com/ , .

Techniques: Medications, Activity Assay, Protease Inhibitor, Neutralization, Inhibition, Blocking Assay