Design, synthesis, and computational studies of inhibitors of Bcl-XL.

  title={Design, synthesis, and computational studies of inhibitors of Bcl-XL.},
  author={Cheol-Min Park and T. Hasegawa M. Oie and Andrew M. Petros and Haichao Zhang and Paul M. Nimmer and Rodger F. Henry and Steven W. Elmore},
  journal={Journal of the American Chemical Society},
  volume={128 50},
One of the primary objectives in the design of protein inhibitors is to shape the three-dimensional structures of small molecules to be complementary to the binding site of a target protein. In the course of our efforts to discover potent inhibitors of Bcl-2 family proteins, we found a unique folded conformation adopted by tethered aromatic groups in the ligand that significantly enhanced binding affinity to Bcl-XL. This finding led us to design compounds that were biased by nonbonding… CONTINUE READING


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