LAUSR

Akt is a protein kinase that has been implicated in the progression of cancerous tumors. A number of covalent allosteric Akt inhibitors are known, and based on these scaffolds, a small library of novel potential covalent allosteric imidazopyridine-based inhibitors was designed and synthesized, with click chemistry enabling a modular approach to a number of these target compounds. Evaluation of the binding modes, potencies and antiproliferative activities of these synthesized compounds was explored, thereby furthering the structure activity relationship knowledge of this class of Akt inhibitors. Three novel covalent inhibitors were identified, exhibiting moderate activity against Akt1 and various cancer cell lines, potentially paving the way for more covalent allosteric inhibitors with improved properties.