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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Keto-1,3,4-oxadiazoles as cathepsin K inhibitors
James T Palmer1, Bernard L Hirschbein, Harry Cheung
1Celera Genomics, Inc., 180 Kimball Way, South San Francisco, CA 94080, USA. jim.palmer@celera.com
Abstract:
We have prepared a series of cathepsin K inhibitors bearing the keto-1,3,4-oxadiazole warhead capable of forming a hemithioketal complex with the target enzyme. By modifying binding moieties at the P1, P2, and prime side positions of the inhibitors, we have achieved selectivity over cathepsins B, L, and S, and have achieved sub-nanomolar potency against cathepsin K. This series thus represents a promising chemotype that could be used in diseases implicated by imbalances in cathepsin K activity such as osteoporosis.
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