azd5363  (TargetMol)

Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: Synergistic anti-tumor effect of LB42708 combined with AKT inhibitor AZD5363 on RAS-mutant NSCLC cells. A and B A549 ( A ) and NCI-H1915 ( B ) were treated with increasing concentrations of LB42708 or 20 µM tipifarnib for 48 h, followed by western blot analysis of the expression and phosphorylation levels of the indicated proteins. C and F Fa-Dose plots showing the growth-inhibitory effects of LB42708 or AZD5363 on A549 ( C ) and NCI-H1915 ( F ) cells. D and G Fa-Dose plots illustrating the synergistic effects of LB42708 combined with AZD5363 on A549 ( D ) and NCI-H1915 ( G ) cell growth. E and H Fa-CI plot indicating synergism between LB42708 and AZD5363 in inhibiting the proliferation of A549 ( E ) and NCI-H1915 ( H ) cells. I and J A549 ( I ) and NCI-H1915 ( J ) cells were treated with 5 or 10 µM LB42708, AZD5363, or their combination for 48 h. The expression and phosphorylation levels of the indicated proteins were analyzed by western blotting. All experiments were independently repeated a minimum of three times. Quantitative data are presented as mean ± SD. Statistical analysis was performed using one-way ANOVA followed by Dunnett’s test. Significance levels were defined as * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001 compared with the control group; ns indicates no statistically significant difference

Article Snippet: Bortezomib and AZD5363 were acquired from Topscience (Shanghai, China).

Techniques: Mutagenesis, Western Blot, Expressing, Phospho-proteomics, Control

Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: LB42708 and AZD5363 combination induces cell arrest at the G2/M or G1phase, and induces apoptosis. A and B Cell cycle distribution was determined by flow cytometry in A549 ( A ) and NCI-H1915 ( B ) cells following treatment with DMSO (control), 5 µM LB42708, 5 µM AZD5363, or their combination for 24 h. Results from three independent experiments were averaged, and the proportions of cells in each phase were plotted to illustrate cell cycle arrest. C and D Flow cytometry was used to assess apoptosis by detecting Annexin V-FITC and propidium iodide (PI) staining after 60 h of drug treatment (10 µM LB42708, 10 µM AZD5363, or their combination). The combined percentages of early and late apoptotic cells were calculated for each treatment group based on the average of three independent experiments and are presented as total apoptotic cell percentages. C A549 cells; D NCI-H1915 cells. E and F A549 ( E ) and NCI-H1915 ( F ) cells were treated with DMSO (control), 10 µM LB42708, 10 µM AZD5363, or their combination for 48 h. The levels of cleaved caspase-3 and caspase-7 were examined by western blotting. Quantitative results represent the average of three independent experiments and are expressed as mean ± SD. Statistical significance was evaluated using one-way ANOVA with Dunnett’s test. Differences versus the control group were considered significant at * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001; ns denotes no significant difference

Article Snippet: Bortezomib and AZD5363 were acquired from Topscience (Shanghai, China).

Techniques: Flow Cytometry, Control, Staining, Western Blot

Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: LB42708 demonstrates cytotoxicity to KRAS-mutant NSCLC PDOs. A Schematic overview for the establishment of lung cancer patient-derived organoids. B and C H&E-stained and IHC-stained images of PDO4 ( B ), PDO6 ( C ) and their original lung cancer tissues. Scale bar = 50 μm. D and E The effects of 15 µM LB42708, 15 µM AZD5363, and their combination on the growth and structural integrity of PDO4 ( D ) and PDO6 ( E ). Representative microscopic images of PDOs morphology before and after 5 days of drug treatment. Scale bars: 200 μm (upper panel), 50 μm (lower panel). F and G IC 50 values of LB42708 for PDO4 ( F ) and PDO6 ( G ). H and I Cell viability of PDO4 ( H ) and PDO6 ( I ) treated with LB42708, AZD5363, or their combination was assessed using a luminescent ATP assay. Results were expressed as the percentage of viable cells relative to untreated spheroids. Bars depict mean ± SD ( n = 4). One-way ANOVA followed by Dunnett’s test was used for statistical analysis. Significance levels vs. the control group were indicated as * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001; ns indicates no significant difference

Article Snippet: Bortezomib and AZD5363 were acquired from Topscience (Shanghai, China).

Techniques: Mutagenesis, Derivative Assay, Staining, ATP Assay, Control

Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: LB42708 inhibits the in vivo growth of RAS-mutant NSCLC tumors. A Schemes for the in vivo experimental procedures to evaluate anticancer activities of LB42708 and AZD5363. To evaluate the enhanced antitumor effect of combined treatment, NCI-H1915 tumor-bearing BALB/c nude mice (injected subcutaneously with 5 × 10⁶ cells per mouse) were administered vehicle, LB42708 (25 mg/kg), AZD5363 (25 mg/kg), or a combination of both via intraperitoneal injection for 15 consecutive days. B Xenograft tumors from each group were collected on day 20 ( n = 6 per group). C Tumor volumes were recorded throughout the study and expressed as mean ± SD ( n = 6 per group). D Final tumor weights were quantified and shown as mean ± SD in a histogram ( n = 6 per group). E Body weights of mice in each group were monitored and plotted over time. F Representative images of endpoint tumor tissues showing: H&E staining for histological features, Ki-67 immunohistochemistry for cell proliferation, and TUNEL staining for apoptosis. Scale bar = 100 μm. G and H Statistics data represent mean ± SD ( n = 6) of Ki67 ( G ) and TUNEL ( H ) for each group. Statistical analysis was performed using one-way ANOVA followed by Dunnett’s test. Comparisons to the control group were marked as * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001; ns indicates no significant difference. I and J A model illustrating the synergistic anti-tumor mechanisms of LB42708 and the AKT inhibitor AZD5363 in RAS-mutant NSCLC ( I ), and the mechanism by which LB42708 enhances the sensitivity of PC9GR cells to gefitinib ( J )

Article Snippet: Bortezomib and AZD5363 were acquired from Topscience (Shanghai, China).

Techniques: In Vivo, Mutagenesis, Injection, Staining, Immunohistochemistry, TUNEL Assay, Control

Journal: Cell Discovery

Article Title: ASCT2 palmitoylation regulated by JNK1-ZDHHC14 axis orchestrates glutamine metabolism and NSCLC progression

doi: 10.1038/s41421-026-00870-z

Figure Lengend Snippet: a NCI-H1299 and NCI-H1975 cells were cultured in the medium with or without glutamine for 12 h, and then the expression levels of ASCT2 and ZDHHC14 were analyzed by western blot. b Palmitoylation effect of glutamine deprivation or H 2 O 2 on ASCT2 in NCI-H1975 cells expressing ASCT2 was examined by immunoprecipitation (IP) and Alkyne-azide click chemistry experiments. c NCI-H1299 (left) and NCI-H1975 (right) cells expressing ASCT2-WT or ASCT2 C39S/C48S mutant were cultured in the medium with or without glutamine for 12 h, and the expression levels of ASCT2 were examined by western blot. d NCI-H1299 cells were cultured in the medium with or without glutamine and treated with addition of 50 μg/mL CHX, harvested at indicated time for western blot. The band density of ZDHHC14 was quantified and normalized to Actin (mean ± SD, n = 3). The p value was determined by two-way ANOVA. e Expression of ASCT2 and ZDHHC14 was analyzed by western blot in NCI-H1299 cells cultured in the medium with or without glutamine and treated with these indicated signaling pathway inhibitors (5 μM LY294002 and 5 μM AZD5363 for inhibiting AKT, 2 μM Dorsomorphin dihydrochloride for inhibiting AMPK, 5 μM Ravoxertinib and 5 μM SCH772984 for inhibiting ERK, 5 μM JNK-IN-8 for inhibiting JNK, 5 μM Adezmapimod and 5 μM SB-202190 for inhibiting p38, and 10 μM MHY1485 for activating mTOR) for 12 h. f NCI-H1299 cells were treated with DMSO, 10 μM MG132, 0.1 μM carf, 25 μM CQ or 0.1 μM BafA1 combined with 0.5 μM Anisomycin for 6 h. g – i ZDHHC14 expression was measured by western blot. NCI-H1299 cells expressing ASCT2-WT ( g ) or ASCT2 C39S/C48S mutant ( h ) were treated with 0.5 μM Anisomycin at the indicated concentrations for 12 h and subjected to western blot with ASCT2, ZDHHC14, JNK1/2/3, Phospho-JNK, and Actin antibodies. ASCT2-Flag expression NCI-H1299 ( i ) and NCI-H1975 cells ( j ) were treated with DMSO or Anisomycin, IP and Alkyne-azide click chemistry experiments examined the effect of Anisomycin on ASCT2 palmitoylation. k NCI-H1299 cells expressing ZDHHC14-Myc were treated with 50 μg/mL CHX and either DMSO or JNK inhibitor (JNK-IN-8), then harvested at indicated time for western blot. The band density of ASCT2 and ZDHHC14 was quantified and normalized to Actin (mean ± SD, n = 3). The p value was determined by two-way ANOVA. l ZDHHC14-knockout cells were co-treated with 50 μg/mL CHX and either DMSO or JNK inhibitor (JNK-IN-8), then harvested at indicated time for western blot. The band density of ASCT2 was quantified and normalized to Actin (mean ± SD, n = 3). The p value was determined by two-way ANOVA.

Article Snippet: JNK-IN-8 (#HY-13319), CC-90001 (#HY-138304), MG132 (#HY-13259), ABD957 (#HY-142161), 2-Bromohexadecanoic acid (2-BP) (#HY-111770), Bafilomycin A1 (BafA1) (#HY-100558), Chloroquine (CQ) (#HY-17589A), Carfilzomib (Carf) (#HY-10455), V9302 (#HY-112683 & #HY-112683A), LY294002 (#HY-10108), AZD5363 (#HY-15431), Ravoxertinib (#HY-15947), SCH772984 (#HY-50846), Adezmapimod (#HY-10256), SB-202190 (#HY-10295), Dorsomorphin dihydrochloride (#HY-13418) and MHY1485 (#HY-B0795) were purchased from MedChemExpress.

Techniques: Cell Culture, Expressing, Western Blot, Immunoprecipitation, Mutagenesis, Knock-Out

Journal: Frontiers in Cell and Developmental Biology

Article Title: Factors that determine cell fate in mitotically arrested cancer cells

doi: 10.3389/fcell.2025.1691574

Figure Lengend Snippet: Time-resolved analysis of HeLa cell responses to mitotic delay in response to KSP and PI3K signaling inhibitors. (A) HeLa cells were cultured in the presence of green fluorescent annexin V and combinations of KSP inhibitor (MSTNH2) and PI3K pathway inhibitors (Akt, AZ5363; PI3K, and LY294002). Apoptosis and cell morphology were monitored hourly by throughput microscopy (four wells per condition and eight data points per well). Disruption of PI3K signaling significantly accelerated apoptosis in HeLa cells undergoing mitotic arrest as compared to cell death in controls, MSTNH2-treated, or PI3K inhibition alone. Error bars represent S.E.M. (B) Selected frames of live-cell imaging of HeLa cells that were untreated (control), cells arrested with MSTNH2 alone, with MSTNH2+ LY294002, or with MSTNH2+ AZD5363, undergoing mitotic arrest and mitotic cell death. Green color denotes early-stage apoptotic cells. Arrowheads highlight individual cells for each sequence. Time denoted in hours: minutes. Bar, 50 µm. (C) Analysis of single-cell behaviors from time-lapse microscopy data in (A) . The duration of mitosis from mitotic entry to cytokinesis (controls) or cell death (MSTNH2-treated, ± PI3K pathway inhibitors) was measured for 55 individual cells per condition, with the mean time in mitosis listed for each condition. ****p < 0.0001.

Article Snippet: To test for potentiation of cell death during mitotic arrest, cells were cultured in MSTNH2 in the presence or absence of the following drugs at concentrations based on the following studies: 20 μM LY294002 (Selleckchem, #S1105) , 20 μM AZD5363 (Selleckchem, #S8019) , 500 nM rapamycin (Selleckchem, #S1039) ( ) and 10 nM defactinib (Selleckchem, #S7654) ( ).

Techniques: Cell Culture, Microscopy, Disruption, Inhibition, Live Cell Imaging, Control, Sequencing, Time-lapse Microscopy

Journal: ImmunoTargets and Therapy

Article Title: Macrophage-Derived Transcriptional Signatures Predict Prognosis and Drug Sensitivity in Thyroid Cancer: Integrative Analysis and Experimental Validation of SMYD3

doi: 10.2147/ITT.S565624

Figure Lengend Snippet: Prediction of immunotherapy response and chemotherapeutic sensitivity based on risk score ( a ) Bar plot showing predicted T-cell exclusion scores from the TIDE algorithm, indicating elevated immune evasion in the high-risk group. ( b ) Scatter plot showing a significant positive correlation between risk score and T-cell exclusion. ( c – f ) Scatter plots demonstrating predicted drug sensitivity (IC50) correlated with risk score for four compounds: Rapamycin, BDP-00009066, AZD5363_1916, and Cediranib_1922. All drugs showed higher predicted sensitivity in high-risk patients (R ≥ 0.2, p < 0.05).

Article Snippet: Cells transfected with si-SMYD3 or si-NC were treated with serial dilutions of Rapamycin (Selleck, Cat# S1039), BDP-00009066 (Aladdin, Cat# B651933), AZD5363_1916 (Selleck, Cat# S8019), or Cediranib_1922 (Aladdin, Cat# C125911).

Techniques:

Journal: ImmunoTargets and Therapy

Article Title: Macrophage-Derived Transcriptional Signatures Predict Prognosis and Drug Sensitivity in Thyroid Cancer: Integrative Analysis and Experimental Validation of SMYD3

doi: 10.2147/ITT.S565624

Figure Lengend Snippet: SMYD3 knockdown reduces sensitivity to high-risk-associated compounds in thyroid cancer cells ( a – d ) Bar plots showing IC50 values for Rapamycin, BDP-00009066, AZD5363_1916, and Cediranib_1922 in thyroid cancer cells with or without SMYD3 knockdown. n = 3. ns = no significance, * p <0.05.

Article Snippet: Cells transfected with si-SMYD3 or si-NC were treated with serial dilutions of Rapamycin (Selleck, Cat# S1039), BDP-00009066 (Aladdin, Cat# B651933), AZD5363_1916 (Selleck, Cat# S8019), or Cediranib_1922 (Aladdin, Cat# C125911).

Techniques: Knockdown