Copanlisib-induced apoptotic cell death is dependent on BCL-xL– and MCL-1–mediated mitochondrial priming. (A) Interaction pattern between proapoptotic BH3 peptides (or BH3 mimetic–ABT-199) and antiapoptotic BCL-2 family members. Red indicates high-affinity binding; green reflects undetectable binding. (B) Illustration of the determination of AUC as a function of cytochrome c release over the dose range of BH3 peptides. (C-D) Correlation between cytochrome c release (indicative of MOMP) induced by HRK (C) or MS-1 (D) peptides (y-axis) and induction of apoptosis after 96-hour exposure to copanlisib (x-axis). Each AUC is an average of 3 biological replicates. Note that BH3 profiling and copanlisib-induced apoptosis were assessed in separate experiments. One-sided P values from the correlation with all tested BH3 peptides were recalculated with the Benjamini-Hochberg procedure and q < 0.1 was considered statistically significant.