Description:
IC50 Value: 41±12 nM (binding to PDEδ in cell) [1]
Deltarasin is a novel and small molecule inhibitor which can inhibit the KRAS-PDEδ interaction and impairs oncogenic KRAS signalling.
Interfering with binding of mammalian PDEδ to KRAS by means of small molecules provides a novel opportunity to suppress oncogenic RAS signalling by altering its localization to endomembranes. Biochemical screening and subsequent structure-based hit optimization yielded inhibitors of the KRAS-PDEδ interaction that selectively bind to the prenyl-binding pocket of PDEδ with nanomolar affinity, inhibit oncogenic RAS signalling and suppress in vitro and in vivo proliferation of human pancreatic ductal adenocarcinoma cells that are dependent on oncogenic KRAS.