tk216  (MedChemExpress)

Journal: bioRxiv

Article Title: Exploring Resistance to ETS Targeting Agents in Diffuse Large B-Cell Lymphoma

doi: 10.1101/2025.09.18.675797

Figure Lengend Snippet: Resistant clones were treated with increasing doses of TK216 (A) or YK-4-279 (B) for 72 hours after 2 weeks of washout from the small molecule to validate the obtained resistance. The figure shows representative results from experiments performed in at least two replicates. C) Cell cycle performed in parental cell line compared to resistant clones after 24 hours of treatment with TK216, 500nM, or DMSO. The figure shows representative results from experiments performed in duplicate.

Article Snippet: TK216, YK-4-279, and tariquidar were purchased from MedChemExpress, zosuriquidar from LubioBioscience, and all the other compounds from Selleckchem.

Techniques: Clone Assay

Journal: bioRxiv

Article Title: Exploring Resistance to ETS Targeting Agents in Diffuse Large B-Cell Lymphoma

doi: 10.1101/2025.09.18.675797

Figure Lengend Snippet: A) Median normalized Log2 expression of genes coding for proteins involved in multi-drug resistance. B) MDR1 expression was obtained with real-time PCR and performed on resistant clones under TK216 or after 2 weeks of washout. Y-axis, Fold change between parental cell lines and resistant clones. C) Protein MDR1 expression with the respective quantification. Representative of two biological replicates. D) Growth curve of cells treated with TK216 or MDR1 inhibitors (tariquidar and zosuriquidar) in single or combination. E) Coefficient of drug interaction (CDI), CDI < 1 = synergism, CDI = 1 = additive, CDI > 1 = antagonism. F) Dose-response curve obtained after 72 hours of treatment with vincristine in parental and resistant clones. The figure shows representative results from experiments performed in duplicate.

Article Snippet: TK216, YK-4-279, and tariquidar were purchased from MedChemExpress, zosuriquidar from LubioBioscience, and all the other compounds from Selleckchem.

Techniques: Expressing, Real-time Polymerase Chain Reaction, Clone Assay

Journal: The Journal of Biological Chemistry

Article Title: Novel markers of MCL1 inhibitor sensitivity in triple-negative breast cancer cells

doi: 10.1016/j.jbc.2024.107375

Figure Lengend Snippet: Inhibition of ETS1 reduces AXL, IL6, and EFEMP1 expression and increases MCL1 inhibitor sensitivity via expression of BCL-2. A , HS578T and MDA231 cells were transfected with control siRNA or ETS1 siRNA for 24 h. B, HS578T and MDA231 cells were treated with vehicle or TK216 (1 μM) for 24 h. mRNA were qPCR analyzed for the indicated genes. Average (triplicate) relative mRNA is presented with SD indicated. Asterisks indicate statistical significance. Representative results of two independent experiments. C , HS578T and MDA231 cells were treated with vehicle, TK216 (1μM), S63845 (1μM), or TK216 + S63845 for 3 days and then analyzed for sub-G1 cells. % sub-G1 cells are presented. Asterisks indicate statistical significance. Representative results of three independent experiments. D , MDA231 cells were treated with vehicle, S63845 (1μM), or S63845 plus BGB324 (1 μM) or TK216 (1μM), for 24 h. Lysates were immunoblotted for the indicated proteins. Representative results of two independent experiments. Original images are presented in Fig. S5 . E , The cells were treated with vehicle or the ERK inhibitor ulixertinib (2 μM) for 24 h. Lysates were immunoblotted for the indicated proteins. Representative results of two independent experiments. Original images are presented in Fig. S6 . F , MDA231 cells were treated with vehicle, S63845 (1 μM), or S63845 plus ABT-199 (2 μM and 5 μM) for 72 h. G , The cells were transfected with control siRNA or the indicated siRNAs against AXL, ETS1, IL6, or EFEMP1 and then treated with vehicle or S63845 for 72 h. Cells were analyzed with FACS for the cell cycle. The average % Sub-G1 cells were presented with SD indicated. Asterisks indicate statistical significance. Representative results of two independent experiments.

Article Snippet: S63845, BGB324, TK216, and paclitaxel were obtained from Selleck Chemicals.

Techniques: Inhibition, Expressing, Transfection, Control

Journal: The Journal of Biological Chemistry

Article Title: Novel markers of MCL1 inhibitor sensitivity in triple-negative breast cancer cells

doi: 10.1016/j.jbc.2024.107375

Figure Lengend Snippet: MCL1 inhibitor-resistant cells have hyper-activation of AXL-JAK/STAT and ERK pathways. AXL inhibitor sensitizes resistant cells. A , lysates of the indicated 8 cell lines were immunoblotted for the indicated proteins with relative signals indicated. Representative results of three independent experiments. Original images are presented in Fig. S3 . B , MDA231 and HS578T cells were treated with vehicle or BG324 (2 μM) for 24 h. Lysates were immunoblotted for the indicated proteins with relative signals indicated. Representative results of three independent experiments. Original images are presented in Fig. S4 . C and D , the indicated 4 cell lines were treated with vehicle, BGB324 (2 μM), S63845 (1 μM for HS578T, MDA231, and MDA468, 0.5 μM for BT20), or BG324+BGB324 for 3 days and then analyzed for sub-G1 (apoptosis) cells. % sub-G1 cells are presented as graphs. Asterisks indicate statistical significance in sensitive cell lines. No significant differences in resistant cell lines. Representative results of three independent experiments.

Article Snippet: S63845, BGB324, TK216, and paclitaxel were obtained from Selleck Chemicals.

Techniques: Activation Assay

Journal: The Journal of Biological Chemistry

Article Title: Novel markers of MCL1 inhibitor sensitivity in triple-negative breast cancer cells

doi: 10.1016/j.jbc.2024.107375

Figure Lengend Snippet: Inhibition of ETS1 reduces AXL, IL6, and EFEMP1 expression and increases MCL1 inhibitor sensitivity via expression of BCL-2. A , HS578T and MDA231 cells were transfected with control siRNA or ETS1 siRNA for 24 h. B, HS578T and MDA231 cells were treated with vehicle or TK216 (1 μM) for 24 h. mRNA were qPCR analyzed for the indicated genes. Average (triplicate) relative mRNA is presented with SD indicated. Asterisks indicate statistical significance. Representative results of two independent experiments. C , HS578T and MDA231 cells were treated with vehicle, TK216 (1μM), S63845 (1μM), or TK216 + S63845 for 3 days and then analyzed for sub-G1 cells. % sub-G1 cells are presented. Asterisks indicate statistical significance. Representative results of three independent experiments. D , MDA231 cells were treated with vehicle, S63845 (1μM), or S63845 plus BGB324 (1 μM) or TK216 (1μM), for 24 h. Lysates were immunoblotted for the indicated proteins. Representative results of two independent experiments. Original images are presented in Fig. S5 . E , The cells were treated with vehicle or the ERK inhibitor ulixertinib (2 μM) for 24 h. Lysates were immunoblotted for the indicated proteins. Representative results of two independent experiments. Original images are presented in Fig. S6 . F , MDA231 cells were treated with vehicle, S63845 (1 μM), or S63845 plus ABT-199 (2 μM and 5 μM) for 72 h. G , The cells were transfected with control siRNA or the indicated siRNAs against AXL, ETS1, IL6, or EFEMP1 and then treated with vehicle or S63845 for 72 h. Cells were analyzed with FACS for the cell cycle. The average % Sub-G1 cells were presented with SD indicated. Asterisks indicate statistical significance. Representative results of two independent experiments.

Article Snippet: S63845, BGB324, TK216, and paclitaxel were obtained from Selleck Chemicals.

Techniques: Inhibition, Expressing, Transfection, Control

Journal: The Journal of Biological Chemistry

Article Title: Novel markers of MCL1 inhibitor sensitivity in triple-negative breast cancer cells

doi: 10.1016/j.jbc.2024.107375

Figure Lengend Snippet: High expressio n of M CL1 correlates with chemoresistance and S63845 sensitizes GS low cells to chemotherapy. A , MCL1 mRNA (GeneChip) correlation with recurrence-free survival in 327 systemically treated patients with TNBC was analyzed with online Kaplan-Meier Plotter software. Note that two of the three different MCL1 probes show similar results that high MCL1 (automatic cutoff) significantly correlates with reduced RFS, while one probe shows a correlation with reduced RFS that is not significant ( p < 0.05). B , The indicated cell lines were treated with vehicle, paclitaxel (PTX), doxorubicin (DOX), S63845, or a combination of S63845 with PTX or DOX for 3 days. Cells were analyzed for sub-G1. Average (triplicate) % apoptotic cells are presented with SD indicated. There are significant differences ( p < 0.05) between single drug and combination treatment in BT20 and MDA468 cells but not in MDA231 and HS578T cells. Representative results of three independent experiments. C , CompuSyn program was used to analyze the synergistic effects of the combination of S63845 (S, μM) with PTX (nM) or DOX (μM). CI value <1 indicates synergistic effects of the indicated drug combinations.

Article Snippet: S63845, BGB324, TK216, and paclitaxel were obtained from Selleck Chemicals.

Techniques: Software