Sonrotoclax is a second-generation BCL2 inhibitor with superior potency and selectivity. (A) Chemical structures of sonrotoclax and venetoclax. The differences are highlighted with light yellow and green ellipses. (B) Cell-free competitive binding assays were performed to measure the disruption of the interaction between the BCL2:BAK-derived peptide by sonrotoclax and venetoclax. (C) SPR binding curves of sonrotoclax and venetoclax. The lines in different colors are the actual curves for the serial concentrations of sonrotoclax (0.625-10 nM) and venetoclax (3.125-200 nM), whereas the corresponding black lines are the fitted curves using the 1:1 binding model. K_D values are presented as the mean values ± standard deviations (SDs) for 4 independent experiments. (D) Inhibition of BCL-xL, BCL-W, MCL-1, and BCL2A1 was measured with a method similar to that described in (B). (E) Measured IC₅₀ values of sonrotoclax and venetoclax for the inhibition of Bcl-2 family members. The data are presented as the mean values ± SDs of 3 independent experiments.