Structure-Based Design of Potent Small-Molecule Inhibitors of Anti-Apoptotic Bcl-2 Proteins

Key Points

• This research aims to design small-molecule inhibitors targeting anti-apoptotic Bcl-2 proteins to induce cancer cell death.
• Structure-based design of inhibitors targeting Bcl-2, Bcl-xL, and Mcl-1.
• Testing binding affinities using K(i) values.
• Evaluating inhibition of cell growth and apoptosis induction in PC-3 prostate cancer cells.
• Compound 5 (TW-37) binds to Bcl-2 with a K(i) of 290 nM and shows high affinity for Bcl-xL and Mcl-1.
• IC(50) for compound 5 is 200 nM, indicating potent inhibition of cell growth.
• Compound 5 induces apoptosis in a dose-dependent manner.