OICR-9429

OICR-9429 is a drug-like experimental small-molecule chemical probe and prototype WDR5 inhibitor developed by the Ontario Institute for Cancer Research (OICR) in collaboration with the Structural Genomics Consortium. It is a highly selective antagonist of the interaction between WD repeat domain 5 (WDR5) and peptide regions of mixed lineage leukemia protein 1 (MLL1) and histone H3, binding to the WIN (WDR5–interaction) arginine-binding pocket on WDR5 and disrupting assembly of SET/MLL histone methyltransferase complexes, thereby suppressing H3K4 trimethylation and downstream oncogenic transcriptional programs.[1][4][5][10] In preclinical models, OICR-9429 selectively impairs proliferation and induces differentiation or apoptosis in certain acute myeloid leukemia subtypes and solid tumors such as breast, colon, pancreatic, and prostate cancers, and can enhance chemosensitivity to agents like cisplatin, but it is currently used as an open-access research tool rather than a clinical-stage therapeutic.[2][5][8][10]