RBM39 degrader REC-1245

An orally bioavailable molecular glue degrader of the splicing factor RNA-binding protein 39 (RNA-binding motif protein 39; RBM39), with potential antineoplastic activity. Upon oral administration, RBM39 degrader REC-1245 induces the ubiquitination and proteasome-mediated degradation of RBM39 via the E3 ligase adaptor DCAF15. This modulates RNA splicing, prevents the expression of certain tumor-associated genes, and downregulates DNA damage response (DDR) networks and cell cycle checkpoints including cyclin-dependent kinase 12 (CDK12), which may inhibit tumor cell proliferation. RBM39, overexpressed in many cancers, plays an important role in alternative splicing and regulating the transcription of many tumor-related genes.