GSK319347A

Description: GSK319347A is a novel, potent and dual inhibitor of TBK1 and IKKepsilon with IC50s of 93 nM and 469 nM, respectively. GSK319347A also inhibits IKK2 with an IC50 of 790 nM. The TBK1/IKK-epsilon enzyme and cell potency of this compound was further improved using structure guided drug design. Systematic exploration of the C6 aryl group led to compound 19, a potent inhibitor of TBK1 with selectivity against cell cycle kinases CDK2 and Aurora B. Further elaboration and optimization gave compound 25, a single digit nM inhibitor of TBK1. These compounds may serve as in vitro probes to evaluate TBK1/IKK-epsilon as an oncology target.

References: Bioorg Med Chem Lett. 2014 Feb 15; 24(4):1138-43.