1. Structure-guided design of a selective BCL-X L inhibitor Structure-guided design of a selective BCL-X L inhibitor Tianlei Sun 2013/11/26

2. Why search for inhibitors of BCL-XL BCL-X L is anti-apoptotic protein. Enhancing apoptotic responses of cancer cells by inhibiting BCL-X L. Instead of inhibiting multiple anti- apoptotic BCL-2 family members, a BCL- X L –selective inhibitor would be expected to minimize the toxicity to normal tissues.

3. How they did High-throughput screen Fig.1 Compound 1a identified from the screen and close analog 1b

4. Fig.2 Two potential binding modes for 1b in the hydrophobic groove of BCL-XL.

5. Fig.3 Structure of compound2. Fig.4 binding mode of 2 in the BCL-X L hydrophobic groove Fig.5 interaction network between the benzothiazole moiety of 2 and Ser106, Asp107 and Leu108 in the P2 pocket.

6. Fig.6 Position of Phe105 in relation to the furan moiety of 2 and the electrostatic interaction between Arg139 and the acylsulfonamide group of 2.

9. Pymol 演示