ggti 298 tfa

GGTI298 Trifluoroacetate (GGTI 298 TFA salt) is a geranylgeranyltransferase I inhibitor with ability to arrest human tumor cells in the G1 phase of the cell cycle and induce apoptosis.

GGTI 2133, a peptidomimetic inhibitor of geranylgeranyl transferase type I (GGTase I; IC50= 38 nM), exhibits 140-fold selectivity towards GGTase I compared to farnesyltransferase (IC50= 5,400 nM). The compound effectively inhibits the geranylgeranylation of RAP1A (IC50= 10 µM) without affecting the farnesylation of H-Ras (IC50= >30 µM). Moreover, GGTI 2133 reduces the growth, migration, and invasion of oral squamous cell carcinoma (OSSC) cells to 75, 45, and 27% of control levels, respectively. When administered intraperitoneally at 5 mg/kg per day, it prevents eosinophil infiltration into the airways in a mouse model of allergic bronchial asthma, although it does not reduce chemokine levels. Additionally, GGTI 2133 thwarts naloxone-induced contraction of ileum in rats experiencing morphine withdrawal syndrome and mitigates the severity of withdrawal symptoms in vivo (ED50= 0.076 mg/kg).

GGTI-286 TFA is a potent, cell-permeable inhibitor of GGTase I, exhibiting 25 times greater effectiveness (IC 50 = 2 μM) compared to the corresponding methyl ester of FTI-276. It specifically targets the geranylgeranylation of Rap1A, demonstrating significant selectivity over the farnesylation of H-Ras in NIH3T3 cells (IC 50s = 2 and >30 μM, respectively). Additionally, GGTI-286 TFA effectively inhibits the stimulation of oncogenic K-Ras4B with an IC 50 of 1 μM.