FGTI-2734

FGTI-2734 is a C-terminal mimetic of Ras and a dual inhibitor of farnesyltransferase (FTase) and geranylgeranyl transferase type I (GGTase I; IC₅₀s = 250 and 520 nM, respectively).¹ It inhibits prenylation of H-Ras and Rap1A in oncogenic H-Ras-transformed NIH3T3 cells (IC₅₀s = 88.7 and 2,700 nM, respectively). FGTI-2734 inhibits membrane localization of K-Ras, which requires prenylation to induce oncogenic transformation, in human MIA PaCa-2 pancreatic and H460 lung cancer cells when used at concentrations of 10 and 30 µM.² It reduces tumor growth, increases intratumoral p53 levels, induces intratumoral apoptosis, and decreases intratumoral HDJ2 farnesylation and Rap1A geranylgeranylation in patient-derived xenograft (PDX) mouse models of mutant KRAS-expressing pancreatic cancer when administered at doses of 50 or 100 mg/kg per day.

WARNING This product is not for human or veterinary use.

1. Fletcher, S., Keaney, E.P., Cummings, C.G., et al. Structure-based design and synthesis of potent, ethylenediamine-based, mammalian farnesyltransferase inhibitors as anticancer agents. J. Med. Chem. 53(19), 6867-6888 (2010).

2. Kazi, A., Xiang, S., Yang, H., et al. Dual farnesyl and geranylgeranyl transferase inhibitor thwarts mutant KRAS-driven patient-derived pancreatic tumors. Clin. Cancer Res. 25(19), 5984-5996 (2019).