Design, synthesis, and activity evaluation of broad-spectrum small-molecule inhibitors of anti-apoptotic Bcl-2 family proteins: characteristics of broad-spectrum protein binding and its effects on anti-tumor activity.

A series of class A compounds which have the basic skeleton of ABT-737 and the h2 residues of Bim BH3 were designed, and showed broad-spectrum binding activity to target proteins similar to that of Bim BH3 peptide. Then class B compounds were synthesized by modifying the structure of the most effective class A compound, A-4, and showed better binding affinity to the target proteins.