FGTI-2734

FGTI-2734 is a dual inhibitor of farnesyltransferase (FTase) and geranylgeranyl transferase type I (GGTase 1), designed to target oncogenic RAS-driven cancers, particularly mutant KRAS-dependent tumors. It is a small molecule that functions as a CAAX tetrapeptide mimetic, blocking RAS membrane localization—a process crucial for the cancer-causing activity of KRAS proteins. By simultaneously inhibiting FTase and GGTase 1, FGTI-2734 prevents cancer cells from bypassing single-pronged inhibitors, thereby overcoming treatment resistance. The compound suppresses oncogenic signaling pathways including PI3K/AKT/mTOR and cMYC, while upregulating the tumor suppressor p53 and inducing apoptosis. FGTI-2734 is effective in various in vivo and ex vivo models, including patient-derived xenografts and samples from pancreatic cancer patients. Developed at H. Lee Moffitt Cancer Center & Research Institute, its main indication has been investigated in preclinical models of pancreatic, lung, and colon cancers driven by mutant KRAS[1][3][5].