GGTI 2133 is a peptidomimetic inhibitor of geranylgeranyl transferase type I (GGTase I; IC₅₀= 38 nM).¹It is 140-fold selective for GGTase I over farnesyltransferase (IC₅₀= 5,400 nM).In vitro, it inhibits geranylgeranylation of RAP1A (IC₅₀= 10 µM) without inhibiting farnesylation of H-Ras (IC₅₀= >30 µM). It also inhibits cell growth and decreases migration and invasion of oral squamous cell carcinoma (OSSC) cells to 75, 45, and 27% of control values, respectively.²GGTI 2133 (5 mg/kg per day, i.p.) prevents ovalbumin-induced eosinophil infiltration into airways in a mouse model of allergic bronchial asthma but does not prevent an increase in chemokines.³It also blocks naloxone-induced contraction of ileum isolated from rats with morphine withdrawal syndrome and dose-dependently decreases withdrawal severityin vivo(ED₅₀= 0.076 mg/kg).⁴

1.Vasudevan, A., Qian, Y., Vogt, A., et al.Potent, highly selective, and non-thiol inhibitors of protein geranylgeranyltransferase-IJ. Med. Chem.42(8)1333-1340(1999) 2.Hamada, M., Miki, T., Iwai, S., et al.Involvement of RhoA and RalB in geranylgeranyltransferase I inhibitor-mediated inhibition of proliferation and migration of human oral squamous cell carcinoma cellsCancer Chemother. Pharmacol.68(3)559-569(2011) 3.Chiba, Y., Sato, S., and Misawa, M.GGTI-2133, an inhibitor of geranylgeranyltransferase, inhibits infiltration of inflammatory cells into airways in mouse experimental asthmaInt. J. Immunopathol. Pharmacol.22(4)929-935(2009) 4.Rehni, A.K., and Signh, T.G.Pharmacological modulation of geranylgeranyltransferase and farnesyltransferase attenuates opioid withdrawal in vivo and in vitroNeuropharmacology7119-26(2013)