Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery
Daniel A Erlanson1, Joseph W Arndt, Mark T Cancilla
1Sunesis Pharmaceuticals, Inc., 395 Oyster Point Blvd., South San Francisco, CA 94080, USA. derlanson@carmot.us
Bioorganic & Medicinal Chemistry Letters
|April 5, 2011
Abstract:
We report the use of a fragment-based lead discovery method, Tethering with extenders, to discover a pyridinone fragment that binds in an adaptive site of the protein PDK1. With subsequent medicinal chemistry, this led to the discovery of a potent and highly selective inhibitor of PDK1, which binds in the 'DFG-out' conformation.
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