Journal: bioRxiv

Article Title: CK2 inhibitor, CX-4945, enhances BH3 priming and promotes apoptosis of venetoclax-resistant AML by targeting antiapoptotic proteins

doi: 10.64898/2025.12.24.696284

Figure Lengend Snippet: A) AML cell lines including both VEN-susceptible and resistant (Molm-13, Molm-13/VR, HL-60, HL-60/VR, U937), and AML PDX cells (2016-1, 2016-7) were treated with different concentrations of CX-4945 and VEN alone or in combination with indicated doses for 48 h. Cell viability was assessed using WST reagent and cell viability was calculated relative to vehicle-treated cells as 100%. B) ZIP synergy scores for CX-4945 and VEN combination in different AML cell lines and PDX cells were shown. ZIP scores greater than 10 indicates ‘synergy’, and 0-10 indicate ‘additive’ activity between CX-4945 and VEN. C-D) AML cells (Molm-13, Molm-13/VR, PDX 2016-7) were treated with CX-4945 and VEN alone or in combination for 24 h and stained with Annexin V/7AAD for analyzing apoptosis by flow cytometry ( C ). Relative apoptosis was calculated by normalizing to vehicle treated cells ( D ). The data are presented as mean ± SD (n=2-4). *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001 by one-way ANOVA (Holm-Sidak’s multiple comparisons test) denotes statistical significance. E) AML cell lines (Molm-13, Molm-13/VR) were treated with CX-4945 and VEN alone or in combination for 24 h and the surface expression of chemoresistance markers (CD47 and CD123) was analyzed by flow cytometry. F) Schematic showing the workflow for dynamic BH3 profiling to measure drug-induced priming of BH3 peptides in AML cells. The difference in Cyt c release (%) with and without drug treatment was presented as delta priming. Created with BioRender.com . G) Molm-13 and Molm-13/VR cells were tested for Cyt C release by priming with BH3 peptides with and without CX-4945 treatment and calculated the delta priming. The data are presented as mean ± SEM (n=2) and analyzed by two-way ANOVA (Sidak’s multiple comparisons test).

Article Snippet: CX-4945 (#HY-50855B) and venetoclax (#HY-15531) were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Activity Assay, Staining, Flow Cytometry, Expressing

Journal: bioRxiv

Article Title: CK2 inhibitor, CX-4945, enhances BH3 priming and promotes apoptosis of venetoclax-resistant AML by targeting antiapoptotic proteins

doi: 10.64898/2025.12.24.696284

Figure Lengend Snippet: A) The common mechanisms that govern cellular MCL-1 levels at transcription, translation, and post-translation levels are depicted. The signaling cascade mediated through CK2, PI3K/AKT, and mTOR regulate transcription and translation of MCL-1 isoforms (L-large, S-short, ES-extra short). MCL-1L (anti-apoptotic) undergoes caspase-mediated cleavage to form pro-apoptotic shorter MCL-1 isoforms (S & ES) that can induce cellular apoptosis independent of BAX and BAK. Created using BioRender.com . B) The levels of MCL-1 isoforms (L and ES) were measured by immunoblotting in AML cell lines and PDX cells after 24h of treatment with CX-4945 and VEN alone or in combination. C) Quantification of MCL-1 transcript levels after treatment with CX-4945 and VEN alone or in combination for 24h in indicated AML cell lines and PDX cells by qRT-PCR. The data are presented as mean ± SD (n=3) and analyzed by two-way ANOVA (Tukey’s multiple comparisons test). *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001 are considered statistically significant. D) Immunoblotting analysis of AML cell lines (Molm-13, Molm-13/VR, U937) and PDX (2016-1, 2016-7) cells after 24h of treatment with CX-4945 and VEN alone or in combination. β-Actin was used as a loading control. Representative blots from two to three independent experiments were shown.

Article Snippet: CX-4945 (#HY-50855B) and venetoclax (#HY-15531) were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Western Blot, Quantitative RT-PCR, Control

Journal: bioRxiv

Article Title: CK2 inhibitor, CX-4945, enhances BH3 priming and promotes apoptosis of venetoclax-resistant AML by targeting antiapoptotic proteins

doi: 10.64898/2025.12.24.696284

Figure Lengend Snippet: A) Schematic depicting the treatment plan in AML patient-derived xenograft (PDX) mouse model. Similar scheme followed for cell line-derived xenograft (CDX) mice except the analysis after two-weeks of treatment. The NRG-S mice were irradiated and intravenously injected with AML cell lines Molm-13VR (0.25×10 6 cells/mouse), U937 (1×10 4 cells/mouse), and PDX 2016-7 (0.5×10 6 cells/mouse) and randomized into experimental groups (Vehicle, CX-4945, VEN, and CX+VEN Como). The drug treatment started after one week of cell transplantation and followed up for survival analysis or analysis after two-weeks of treatment (only for PDX). B-F) After two weeks of drug treatment, mice injected with PDX 2016-7 cells were sacrificed and spleen weight was recorded ( B ). The cells collected from spleens were analyzed by flow cytometry to analyze percent hCD45 positive cells ( C ). D-F) CBC analysis was performed on PDX 2016-7 mice after two-weeks of drug treatment by Hemavet analyzer. The data for B-F are presented as mean ± SD (n=7-8) and analyzed by one-way ANOVA (Tukey’s multiple comparisons test). *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001 indicates statistical significance, while ‘ns’ denotes ‘not significant’. G) Immunoblotting analysis of spleen cells collected from PDX 2016-7 mice after two-weeks of treatment with CX-4945, VEN, and CX+VEN combo. The data for three different experimental animals was presented. H-J) Kaplan-Meyer survival analysis of 2016-7 PDX ( H ), Molm-13/VR CDX ( I ), and U937 CDX ( J ) mice after treatment with CX-4945, VEN and CX+VEN combo. The overall median survival (MS) days for each experimental group of PDX and CDX mice were provided next to the legend. *p<0.05, **p<0.01 and ***p<0.001 by Gehan-Breslow-Wilcoxon test indicates statistical significance.

Article Snippet: CX-4945 (#HY-50855B) and venetoclax (#HY-15531) were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Derivative Assay, Irradiation, Injection, Transplantation Assay, Flow Cytometry, Western Blot

Journal: bioRxiv

Article Title: CK2 inhibitor, CX-4945, enhances BH3 priming and promotes apoptosis of venetoclax-resistant AML by targeting antiapoptotic proteins

doi: 10.64898/2025.12.24.696284

Figure Lengend Snippet: A) AML cells from patients were surfaced stained with different fluorescent labeled antibodies and analyzed for the expression of markers for LSCs (CD34, CD38, TIM3) and chemoresistance (CD47 and CD123) by flow cytometry. B) The basal level expression of CK2α, BCL-XL, and CK2 activity (p-CK2 substrate) was measured in primary AML cells by immunoblotting analysis. C) The basal level apoptosis and viability of primary AML patient cells was assessed after 12-24h of post-thaw using Annexin V & dead cell kit for Muse cell analyzer. The patient cells with high basal level apoptosis were omitted and the ones used for further testing were highlighted using red square box. D & E) AML patient cells were treated with CX-4945 and VEN alone and in combination for 24 h and surface stained for different cell surface markers along with annexin V. The relative apoptosis in bulk cells ( D ), LSCs (CD34+CD38−) and chemoresistant (CD47+CD123-) subpopulations were calculated by normalizing the percent apoptosis in vehicle treated cells ( E ). The data are presented as mean ± SEM (n=6-7) and analyzed via one-way ANOVA (Tukey’s multiple comparisons test). *p<0.05, **p<0.01, and ***p<0.001 considered as statistically significant.

Article Snippet: CX-4945 (#HY-50855B) and venetoclax (#HY-15531) were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Staining, Labeling, Expressing, Flow Cytometry, Activity Assay, Western Blot

Journal: bioRxiv

Article Title: CK2 inhibitor, CX-4945, enhances BH3 priming and promotes apoptosis of venetoclax-resistant AML by targeting antiapoptotic proteins

doi: 10.64898/2025.12.24.696284

Figure Lengend Snippet: Inhibition of CK2-mediated signaling through CX-4945 negatively affect cell survival pathways (PI3K/AKT/mTOR, NF-κB pathways) and anti-apoptotic proteins (MCL-1L and BCL-XL). Downregulation of anti-apoptotic BCL2 members (MCL-1L, BCL-XL) further enhance BCL-2 dependency and enhance VEN-mediated apoptosis in VR-AML cells. Overexpression of pro-apoptotic MCL-1ES isoform that can mediate mitochondrial depolarization independent of BAX/BAK contribute to potentiate VEN activity. Moreover, the transcriptome of VR-AML cells followed by CX-4945 and VEN combination treatment showed reversal of molecular gene signatures associated with VEN resistance and result in potentiated apoptosis in VR-AML cells. The signaling targeted by CX-4945 and VEN are represented by dotted lines. Created using BioRender.com .

Article Snippet: CX-4945 (#HY-50855B) and venetoclax (#HY-15531) were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Inhibition, Over Expression, Activity Assay

Journal: CNS Neuroscience & Therapeutics

Article Title: Targeting AKT and CK2 represents a novel therapeutic strategy for SMO constitutive activation‐driven medulloblastoma

doi: 10.1111/cns.13835

Figure Lengend Snippet: Synergetic effects of CX4945 and MK2206 for MB cells with SMO W535L . (A) Measurement of combination index of CX4945 plusMK2206 in three MB cells with SMO W535L . (B) Colony formation of three MB cells with SMO W535L in treatment of CX4945 or/and MK2206. The data are shown as mean ± SD; *** p < 0.001; ** p < 0.01; n = 4 per group. (C) Western blotting of MB cells expressing flag tagged SMO W535L treated with indicated reagents. (D) Representative images of orthotopic growth of ONS76 cells with SMO W535L treated with vehicle, CX4945, MK2206, or MK+CX). (E) Statistic graph of tumor size using bioluminescence signal intensity. The data are shown as mean ± SD; *** p < 0.001; ** p < 0.01; n = 8 per group. (F) Kaplan–Meier survival analysis of mice treated with indicated conditions. n = 8 per group

Article Snippet: SAG (SMO agonist) (#S7779) (0.1 μM), GDC‐0449 (#S1082) (1 μM), NVP‐LDE225 (#S2151) (1 μM), CX4945 (#S0707), and MK2206 (#S1078) were purchased from Selleck ( https://www.selleck.cn/ ).

Techniques: Western Blot, Expressing

Journal: Dr. Sulaiman Al Habib Medical Journal

Article Title: In Silico Identification of Potential Inhibitors of the SARS-CoV-2 Nucleocapsid Through Molecular Docking-Based Drug Repurposing

doi: 10.1007/s44229-022-00004-z

Figure Lengend Snippet: Molecular docking results of 20 antiviral NTD of N protein inhibitors

Article Snippet: Silmitasertib was developed by Senhwa Biosciences to treat cancers, such as pediatric brain tumors, medulloblastoma, and bile duct cancer.

Techniques: Binding Assay

Journal: Dr. Sulaiman Al Habib Medical Journal

Article Title: In Silico Identification of Potential Inhibitors of the SARS-CoV-2 Nucleocapsid Through Molecular Docking-Based Drug Repurposing

doi: 10.1007/s44229-022-00004-z

Figure Lengend Snippet: Molecular docking interactions and orientations of the top five anti-N drugs with the SARS-CoV-2 N-NTD. Docking interactions of A silmitasertib, B nintedanib, and C ternatin. The right panel shows a schematic representation of interactions of these drug molecules with the N-NTD. The protein residues and interactions are colored accordingly and provided in the figure

Article Snippet: Silmitasertib was developed by Senhwa Biosciences to treat cancers, such as pediatric brain tumors, medulloblastoma, and bile duct cancer.

Techniques:

Journal: Dr. Sulaiman Al Habib Medical Journal

Article Title: In Silico Identification of Potential Inhibitors of the SARS-CoV-2 Nucleocapsid Through Molecular Docking-Based Drug Repurposing

doi: 10.1007/s44229-022-00004-z

Figure Lengend Snippet: Molecular docking results of the top five antiviral CTD of N protein inhibitors

Article Snippet: Silmitasertib was developed by Senhwa Biosciences to treat cancers, such as pediatric brain tumors, medulloblastoma, and bile duct cancer.

Techniques: Binding Assay

Journal: Dr. Sulaiman Al Habib Medical Journal

Article Title: In Silico Identification of Potential Inhibitors of the SARS-CoV-2 Nucleocapsid Through Molecular Docking-Based Drug Repurposing

doi: 10.1007/s44229-022-00004-z

Figure Lengend Snippet: Molecular docking interactions and orientations of the top five anti-N drugs with the SARS-CoV-2 C-CTD. Docking interactions of A silmitasertib, B sirolimus-rapamycin, and C dovitinib. The right panel shows a schematic representation of interactions of these drug molecules with the C-CTD. The protein residues and interactions are colored accordingly and provided in the figure

Article Snippet: Silmitasertib was developed by Senhwa Biosciences to treat cancers, such as pediatric brain tumors, medulloblastoma, and bile duct cancer.

Techniques:

Journal: Dr. Sulaiman Al Habib Medical Journal

Article Title: In Silico Identification of Potential Inhibitors of the SARS-CoV-2 Nucleocapsid Through Molecular Docking-Based Drug Repurposing

doi: 10.1007/s44229-022-00004-z

Figure Lengend Snippet: Drug–gene network constructed with STITCH. The edge width of protein–drug interactions is scaled according to the binding affinity between the drug and the protein. The drug–protein networks of A dovitinib, B fedratinib, C luteolin, D nintedanib, E rapamycin, and F silmitasertib

Article Snippet: Silmitasertib was developed by Senhwa Biosciences to treat cancers, such as pediatric brain tumors, medulloblastoma, and bile duct cancer.

Techniques: Construct, Binding Assay

Journal: Molecular Oncology

Article Title: Endothelin‐converting enzyme‐1c promotes stem cell traits and aggressiveness in colorectal cancer cells

doi: 10.1002/1878-0261.12609

Figure Lengend Snippet: Mutation of Lys‐6 to Arg enhances stability of ECE1c. (A) DLD‐1 clone cells expressing Flag‐tagged ECE1c WT or ECE1c K6R proteins were incubated with 20 μg·mL −1 cycloheximide (CHX) in the absence (for 36 h) or presence (for 12 h) of 25 μ m silmitasertib. ECE1c proteins were detected by western blot with an anti‐Flag antibody, using β‐actin as loading control. Representative blots are shown (upper). Relative levels (%) of Flag‐ECE1c proteins from three independent experiments were calculated (lower). (B) DLD‐1 clones described in A were grown in medium without FBS for 48 h. Culture supernatants were used to measure ET‐1 levels using ELISA according to manufacturer’s instructions (Thermo Fisher). Data represent average ± SEM ( n = 3). ANOVA and Tukey tests were used. * P ≤ 0.05, ** P ≤ 0.01.

Article Snippet: Cells (5 × 10 5 ) were seeded into P60 plates and cultured for 36 h in complete medium under normal conditions, with 20 μg·mL −1 cycloheximide (CHX) in the absence or presence of 25 μ m silmitasertib (ApexBio Technology LLC, Houston, TX, USA).

Techniques: Mutagenesis, Expressing, Incubation, Western Blot, Clone Assay, Enzyme-linked Immunosorbent Assay

Journal: bioRxiv

Article Title: Adjuvant Discovery via a High Throughput Screen using Human Primary Mononuclear Cells

doi: 10.1101/2022.06.17.496630

Figure Lengend Snippet: Selection criteria for the top screening hits include demonstrations of titratability, robust efficacy in inducing multiple cytokines, and satisfactory potency. Chemical structure, well identification, and multiplexed concentration titration experimental data shown for these top screening hits: A. Lexibulin, B. Amphotericin, C. Silmitasertib, and D. Vinblastine.

Article Snippet: Silmitasertib , Fisher Scientific , Item Code: 501873883.

Techniques: Selection, Concentration Assay, Titration

Journal: bioRxiv

Article Title: Adjuvant Discovery via a High Throughput Screen using Human Primary Mononuclear Cells

doi: 10.1101/2022.06.17.496630

Figure Lengend Snippet: Key resource table

Article Snippet: Silmitasertib , Fisher Scientific , Item Code: 501873883.

Techniques: Recombinant, Sterility, Injection, Modification, Staining, Saline, Enzyme-linked Immunosorbent Assay, Multiplex Assay, Software