TRPH-395 is a novel small molecule inhibitor that disrupts WDR5 protein-protein interactions. WDR5, a WD repeat family protein, has an established role in leukemia and lymphoma through its association with histone methyltransferase complexes. WDR5 inhibition results in epigenetic modification of histones, disrupting pro-cancer histone methylation. This targeted approach to inhibit histone methylation is predicted to result in a more favorable therapeutic index and improved tolerability in comparison with global hypomethylating agents (HMA).
Pre-clinical data demonstrate broad anti-proliferative activity across a wide range of cancer cell lines, offering potential for clinical utility in solid tumors as well as hematological cancers. The unique targeting approach to disrupting protein-protein interactions for epigenetic modification provides the opportunity for a first-in-class cancer therapy. TRPH-395 is currently in late lead optimization.