SM09419

SM09419 is a small molecule pan-CLK/DYRK inhibitor developed by Biosplice Therapeutics and its subsidiary TenaRx. As a structural analogue of cirtuvivint (SM08502), it functions by inhibiting CDC-like kinases (CLK) and dual-specificity tyrosine-regulated kinases (DYRK), which are critical for the phosphorylation of splicing factors. This inhibition leads to the modulation of alternative RNA splicing, specifically causing the mis-splicing of key oncogenic drivers such as TCF/LEF and BRD9. SM09419 has demonstrated pre-clinical efficacy in models of pediatric cancers, including malignant rhabdoid tumors and medulloblastoma, by inducing cell cycle arrest and apoptosis while suppressing Wnt/beta-catenin signaling and non-canonical BAF (ncBAF) complex function.