GGTI-2418

GGTI-2418 is a highly potent, competitive, and selective geranylgeranyltransferase I (GGTase I) inhibitor. GGTI-2418 inhibits GGTase I and FTase activities with IC₅₀s of 9.5 nM and 53 μM, respectively. GGTI-2418 also increases p27(Kip1) and induces significant regression of breast tumors^[1]. IC50 & Target: IC50: 9.5 nM (GGTase I), 53 μM (FTase)^[1] In Vitro: GGTI-2418 inhibits GGTase I and FTase activities with IC₅₀s of 9.5±2.0 nM and 53±11 μM, respectively, a 5,600-fold selectivity toward inhibition of GGTase I versus FTase. GGTI-2418 demonstrates competitive inhibition of GGTase I against the H-Ras-CVLL protein with a K_i of 4.4±1.6 nM^[1].
GGTi-2418 (10-15 μM; 16 hours) treatment delocalizes FBXL2 and stabilizes IP3R3^[2]. In Vivo: GGTI-2418 (100 mg/kg daily or 200 mg/kg every third day; 15 days) significantly inhibits the growth of breast tumor xenografts in nude mice with MDA-MB-231 xenografts^[1].
GGTI-2418 (100 mg/kg daily; 5 days) induces regression of ErbB2-driven mammary tumors in ErbB2 transgenic mice^[1].
GGTI-2418 inhibits the geranylgeranylation of Rap1 and causes a dramatic decrease in S473 phosphorylation of Akt. GGTI-2418 also upregulates p27 levels in vivo^[1].