The serine threonine kinase Akt regulates cell survival, inhibits apoptosis and is often up-regulated or over-expressed in a number of human tumors. Consequently, interfering with signaling along the PI3K/Akt pathway has been a topic of interest in drug discovery. Herein, we describe the identification and SAR exploration of a thiadiazole series of Akt kinase inhibitors. Guided by structure-based design, the series was optimized to afford Akt inhibitors with single digit nanomolar activity. Pathway inhibition and anti-proliferative effects of these inhibitors have been demonstrated, both in vitro and in vivo.

Structure-based optimization of potent, aminothiadiazole inhibitors of Akt1

246th National Meeting (2013)

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