LJI308

LJI308 is a potent and selective small molecule inhibitor of the p90 ribosomal S6 kinase (RSK) family, including RSK1, RSK2, and RSK3. Developed by Novartis, it is primarily utilized as a pharmacological research tool to investigate the role of RSK signaling in cell proliferation, survival, and therapeutic resistance. In glioblastoma models, LJI308 has been shown to stabilize the transcriptional repressor Capicua (CIC) by preventing its RSK-mediated phosphorylation and subsequent degradation. This stabilization leads to the downregulation of oncogenic transcription factors such as ETV1, ETV4, and ETV5. Research indicates that inhibiting p90RSK with LJI308 can sensitize glioma stem-like cells to MEK/ERK pathway inhibition (e.g., with selumetinib), suggesting a potential strategy for overcoming resistance to RTK/MEK/ERK targeted therapies in aggressive brain tumors.