Discovery of novel inhibitors of anti-apoptotic Bcl-2 proteins derived from Bim BH3 domain

A series of peptides derived from Bim BH3 domain were synthesized and the in vitro binding affinity on anti-apoptotic Bcl-2 proteins and cell killing activity were evaluated. Of particular interest were the analogue SM-5 (KD = 9.48 nmol/L for Bcl-2) and SM-6 (KD = 0.08 nmol/L for Bcl-xL), which exhibited improved binding affinity compared with the lead Bim (KD = 16.90 nmol/L for Bcl-2 and 22.2 nmol/L for Bcl-xL, respectively). Promising inhibitors of anti-apoptotic Bcl-2 proteins might be designed based on the active core.