Towards a RIOK2 Chemical Probe: Cellular Potency Improvement of a Selective 2-(Acylamino)pyridine Series

RIOK2 is an understudied kinase associated with a variety of human cancers including non-small cell lung cancer and glioblastoma. No potent, selective, and cell-active chemical probe currently exists for RIOK2. Such a reagent would expedite research into the biological functions of RIOK2 and validate it as a therapeutic target. Herein, we describe the synthesis of naphthyl-pyridine based compounds that have both improved cellular activity while maintaining selectivity for RIOK2.