| Description | GGTI-2418 is a highly potent, competitive, and selective inhibitor of geranylgeranyltransferase I (GGTase I), showing inhibitory activities with IC50 values of 9.5 nM for GGTase I and 53 μM for FTase, respectively. Additionally, it enhances p27(Kip1) expression and induces significant regression of breast tumors. |
| In vitro | GGTI-2418 demonstrates competitive inhibition of GGTase I against the H-Ras-CVLL protein with a Ki of 4.4±1.6 nM.?GGTi-2418 (10-15 μM;?16 hours) treatment delocalizes FBXL2 and stabilizes IP3R3.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. |
| In vivo | 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.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. |
| Target activity | FTase:53 μM , GGTase I:9.5 nM |
| molecular weight | 441.52 |
| Molecular formula | C23H31N5O4 |
| CAS | 501010-06-6 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 125 mg/mL (283.11 mM), Sonication is recommended. |
| References | 1. Kazi A, et al. Blockade of protein geranylgeranylation inhibits Cdk2-dependent p27Kip1 phosphorylation on Thr187 and accumulates p27Kip1 in the nucleus: implications for breast cancer therapy. Mol Cell Biol. 2009 Apr;29(8):2254-63. 2. Kuchay S, et al. PTEN counteracts FBXL2 to promote IP3R3- and Ca |