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 IC 50 s of 9.5 nM and 53 μM, respectively. GGTI-2418 also increases p27(Kip1) and induces significant regression of breast tumors

In Vitro

GGTI-2418 inhibits GGTase I and FTase activities with IC 50 s 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. GGTi-2418 (10-15 μM; 16 hours) treatment delocalizes FBXL2 and stabilizes IP3R3. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: HeLa cells Concentration: 10-15 μM Incubation Time: 16 hours Result: Delocalized FBXL2 and stabilized IP3R3.

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 . GGTI-2418 (100 mg/kg daily; 5 days) induces regression of ErbB2-driven mammary tumors in ErbB2 transgenic mice . 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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Nude mice implanted with MDA-MB-231 breast cancer tumors Dosage: 100 mg/kg daily or 200 mg/kg every third day Administration: Injected intraperitoneally; 15 days Result: Inhibited the growth of breast tumor xenografts. Animal Model: ErbB2 transgenic mice Dosage: 100 mg/kg/day Administration: Subcutaneously; 5 days Result: Halted tumor growth and induced massive tumor regression. Tumor decreased by 76% following GGTI-2418 treatment.

Form:Solid

IC50& Target:IC50: 9.5 nM (GGTase I), 53 μM (FTase)