Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery
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 hig
Erlanson, Daniel A.,Arndt, Joseph W.,Cancilla, Mark T.,Cao, Kathy,Elling, Robert A.,English, Nicki,Friedman, Jessica,Hansen, Stig K.,Hession, Cathy,Joseph, Ingrid,Kumaravel, Gnanasambandam,Lee, Wen-Cherng,Lind, Ken E.,McDowell, Robert S.,Miatkowski, Konrad,Nguyen, Christine,Nguyen, Thinh B.,Park, Sophia,Pathan, Nuzhat,Penny, David M.,Romanowski, Michael J.,Scott, Daniel,Silvian, Laura,Simmons, Robert L.,Tangonan, Bradley T.,Yang, Wenjin,Sun, Lihong