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Published on: March 5, 2018
Structure-based combinatorial library design: discovery of non-peptidic inhibitors of caspases 3 and 8
1Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA. Martha_S_Head@sbphrd.com
Abstract:
Structure-based design of a combinatorial array was carried out in order to identify non-peptidic thiomethylketone inhibitors of caspases 3 and 8. Five compounds from the designed array were active against caspase 3, and two were active against caspase 8. A 2.5-A resolution co-crystal structure of caspase 3 and a thiomethylketone array member is reported. The structure-based design strategy has proved useful for identifying caspase inhibitors.
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