DELTARASIN TRIHYDROCHLORIDE

Biochem/physiol Actions

Deltarasin is a membrane-permeable benzimidazole derivative that effectively abolishes cellular KRas plasma membrane localization (5 µM for 1 hr) by blocking KRas-PDEδ interaction via high affinity interaction with PDEδ prenyl-binding pocket (K_D = 38 nM). Deltarasin inhibits oncogenic KRas-dependent proliferation (by ~50% of Panc-Tu-I cells; 5µM for 70 hrs) and survival (52% and 46% death induction of Panc-Tu-I and Capan-1 cells, respectively; 5µM for 24 hrs) in human pancreatic ductal adenocarcinoma (PDAC) cultures and is efficacious against Panc-Tu-I xenograft-derived tumor growth in mice in vivo (60% and 80% retardation on day 9, respectively, with 15 mg/kg q.d. or 10 mg/kg b.i.d. via i.p.).