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GGTI-286 is a potent, cell-permeable, and selective inhibitor of GGTase I. This methyl ester derivative of GGTI-287 is about 25-fold more potent than FTI-277 in inhibiting the processing of the geranylgeranylated protein Rap1A. GGTI-286 has also been shown to have a significant antiproliferative effect in human malignant glioma cells. It also selectively antagonizes oncogenic K-Ras4B.
1. Lerner, E C., et al., 1995. Disruption of oncogenic K-Ras4B processing and signaling by a potent geranylgeranyltransferase I inhibitor. The Journal of biological chemistry. 270(45): 26770-3. PMID: 7592913
2. Lerner, E C., et al., 1997. Inhibition of the prenylation of K-Ras, but not H- or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a farnesyltransferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines. Oncogene. 15(11): 1283-8. PMID: 9315095
3. Qian, Y., et al., 1998. Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics. Bioorganic & medicinal chemistry. 6(3): 293-9. PMID: 9568283
4. Bredel, M., et al., 1998. Inhibition of Ras and related G-proteins as a therapeutic strategy for blocking malignant glioma growth. Neurosurgery. 43(1): 124-31; discussion 131-2. PMID: 9657198
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