Journal: iScience

Article Title: Inhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746

doi: 10.1016/j.isci.2024.110961

Figure Lengend Snippet: BTK inhibitors synergize with LU-102 in cells that do not express BTK (A) The expression of active (phosphorylated) BTK and total BTK was determined by western blots. (B) Heatmaps summarizing effects of 48 h co-treatments of MM1.S, MDA-MB-231, and SUM149 cells with BTK inhibitors and sub-toxic concentrations of LU-102 indicated on top of each graph. A single-row heatmaps summarize cell response to 2-fold serial dilutions of LU-102 in the absence of BTK inhibitors. Raw data are presented in Figure S2 A ( n > 3). The bottom graphs show combination indices. (C) Detailed analysis of effects of CGI-1746/LU-102 combination on MDA-MB-231 cells. Cell viability data on the left graph were used to generate the left heatmap in (A) and is also presented in Figure S2 A ( n = 3). Apoptosis of cells treated with 10 μM CGI-1746, and 3 μM LU-102 was determined by flow cytometry using caspase 3/7 probe (middle) and by measuring caspase 3/7 in extracts using Ac-DEVD-AMC (right; n = 3). Error bars represent S.E.M. (D) MDA-MB-231 cells were pulse-treated with carfilzomib for 1 h, after which carfilzomib-containing media was replaced with drug-free media or media containing sub-toxic concentrations of CGI-1746, GDC-0853, and ibrutinib. 48 h after treatment, viability was determined by Alamar Blue ( n = 3). Combination indices were determined as on Figure 1 A.

Article Snippet: INA-6 cells were obtained from DSMZ, and SUM149 cells were obtained from Asterand.

Techniques: Expressing, Western Blot, Flow Cytometry

Journal: iScience

Article Title: Inhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746

doi: 10.1016/j.isci.2024.110961

Figure Lengend Snippet:

Article Snippet: INA-6 cells were obtained from DSMZ, and SUM149 cells were obtained from Asterand.

Techniques: Purification, Virus, Recombinant, Staining, Kinase Assay, RNA Sequencing Assay, Western Blot, Software