CDK9 inhibitors are highly effective at inducing apoptosis in Bfl-1+ lymphomas. (A) AZD4573 and AZD5991 6-hour caspase negative logarithmic 50% effective concentration (pEC50) correlation across 52 lymphoma cell lines. Dots represent individual cell lines, colored by Bfl-1− (blue) or Bfl-1+ (red) protein expression as determined from western blot analysis. Solid and dashed lines illustrate y = x (1:1) and y = x−1 (1:10) axis unity, respectively. (B) Apoptotic sensitivity of lymphoma cell lines to AZD4573 after 6-hour treatment assessed by caspase EC50 determination. (C) Kinetics of MOMP in Bfl-1+ lymphomas over time following incubation with 0.1 µM AZD4573 or 0.5 µM AZD5991, respectively. (D) Western blot analysis for Bfl-1 and Mcl-1 protein expression in MV411 parental, pLVXIP-Flag-empty vector or pLVXIP-Flag-BCL2A1 cell lines. Loading control, vinculin. (E) AZD5991 (left graph) and AZD4573 (right graph) were treated at the indicated concentrations for 6 hours followed by caspase-3/7 measurement in MV411 pLVXIP-Flag-EV or pLVXIP-Flag-BCL2A1 stable cell lines. ns, no significance.