GGTI298 (Trifluoroacetate)

GGTI298 Trifluoroacetate is a CAAZ peptidomimetic geranylgeranyltransferase I (GGTase I) inhibitor, which can inhibit Rap1A with IC₅₀ of 3 μM; little effect on Ha-Ras with IC₅₀ of >20 μM. IC50 & Target:IC50: 3 μM (Rap1A, in vivo), > 20 μM (Ha-Ras, in vivo)^[3] In Vitro: RhoA inhibitor (GGTI298 Trifluoroacetate) significantly reduces cAMP agonist-stimulated apical K+ conductance^[1]. Knockdown of DR4 abolishes NF-κB activation, leading to sensitization of DR5-dependent apoptosis induced by the combination of GGTI298 Trifluoroacetate and TRAIL. GGTI298 Trifluoroacetate/TRAIL activates NF-κB and inhibits Akt. Knockdown of DR5, prevents GGTI298/TRAIL-induced IκBα and p-Akt reduction, suggesting that DR5 mediates reduction of IκBα and p-Akt induced by GGTI298/TRAIL. In contrast, DR4 knockdown further facilitates GGTI298/TRAIL-induced p-Akt reduction^[2]. In Vivo: The vivo mouse ileal loop experiments show fluid accumulation is reduced in a dose-dependent manner by TRAM-34, GGTI298 Trifluoroacetate, or H1152 when inject together with cholera toxin into the loop^[1].