ETC-501

ETC-501 is a potent, selective, and brain-penetrant small molecule inhibitor of MAP kinase-interacting serine/threonine-protein kinases 1 and 2 (MNK1/2). Developed by the Experimental Drug Development Centre (EDDC) at A*STAR in collaboration with Duke-NUS Medical School, the National Neuroscience Institute, and BeiGene, ETC-501 is being investigated for the treatment of glioblastoma (GBM). The drug targets MNK-mediated signaling to inhibit critical oncogenic processes, including MYC-driven transcriptional programs, ribosome biogenesis, and DNA replication. Preclinical studies indicate that ETC-501 acts as both a senescence inducer and a senomorphic agent; when combined with temozolomide (TMZ), it enhances TMZ-induced senescence and suppresses the pro-tumorigenic senescence-associated secretory phenotype (SASP). This approach sensitizes GBM cells to senolytic therapy (e.g., navitoclax), facilitating the clearance of residual senescent cells that might otherwise drive tumor recurrence.