Figure 5. Synergistic co-targeting Mcl-1 and Bcl-2/xL.

(A) VAL and OCI-LY3 cells were subjected to functional screening assay as described in the methods. IC₅₀ values were calculated (represented in the color gradient). Drugs of interests that exhibit synergism or antagonism with AZD5991 are shown. (B, C) DLBCL cells were treated with drugs as indicated for 48 h. Cell proliferation was measured in an MTS assay; % viable cells were normalized to DMSO-treated control. (D) OCI-LY3 cells were treated with AZD5991 and AZD4320 for 48 h. Bliss analysis was conducted to determine the synergistic score. (E) MCL cells were treated with drugs as indicated for 48 h. Cell proliferation was measured in an MTS assay; % viable cells were normalized to DMSO-treated control. (F) Genetically manipulated DLBCL cells were treated with venetoclax and AZD5991 for 48 hours. Cell proliferation was measured in an MTS assay. % viable cells were normalized to DMSO-treated control. ** - p<0.05 vs. untreated control. * - p<0.05 vs. NT (non-targeting sgRNA).