GGTI 2133 (trifluoroacetate salt)

GGTI 2133 is a peptidomimetic inhibitor of geranylgeranyl transferase type I (GGTase I; IC₅₀ = 38 nM). 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. 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. 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).