GGTI 2133 (trifluoroacetate salt)

GGTI 2133 is a peptidomimetic inhibitor of geranylgeranyl transferase type I (GGTase I; IC₅₀ = 38 nM).¹ It 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.² GGTI 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.³ It also blocks naloxone-induced contraction of ileum isolated from rats with morphine withdrawal syndrome and dose-dependently decreases withdrawal severity in vivo (ED₅₀ = 0.076 mg/kg).⁴

WARNING This product is not for human or veterinary use.

1. Vasudevan, A., Qian, Y., Vogt, A., et al. Potent, highly selective, and non-thiol inhibitors of protein geranylgeranyltransferase-I. J. 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 cells. Cancer 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 asthma. Int. 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 vitro. Neuropharmacology 71, 19-26 (2013).