A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion

• Protein expression/activity of ROCK1 and ROCK2 is upregulated in lung tumor tissues.
• DJ4 is a novel, selective inhibitor of ROCK1/2 and MRCKα/β.
• DJ4 effectively inhibits migration and invasion of multiple cancer cell lines.

Two structurally related protein kinase families, the Rho kinases (ROCK) and the myotonic dystrophy kinase-related Cdc42-binding kinases (MRCK) are required for migration and invasion of cancer cells. We hypothesized that simultaneous targeting of these two kinase families might represent a novel therapeutic strategy to block the migration and invasion of metastatic cancers. To this end, we developed DJ4 as a novel small molecule inhibitor of these kinases. DJ4 potently inhibited activities of ROCK and MRCK in an ATP competitive manner. In cellular functional assays, DJ4 treatment significantly blocked stress fiber formation and inhibited migration and invasion of multiple cancer cell lines in a concentration dependent manner. Our results strongly indicate that DJ4 may be further developed as a novel anti-metastatic chemotherapeutic agent for multiple cancers.