[HTML][HTML] Ras CAAX peptidomimetic FTI-277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras-Raf complexes
EC Lerner, Y Qian, MA Blaskovich, RD Fossum… - Journal of Biological …, 1995 - ASBMB
Ras-induced malignant transformation requires Ras farnesylation, a lipid posttranslational
modification catalyzed by farnesyltransferase (FTase). Inhibitors of this enzyme have been
shown to block Ras-dependent transformation, but the mechanism by which this occurs
remains largely unknown. We have designed FTI-276, a peptide mimetic of the COOH-
terminal Cys-Val-Ile-Met of K-Ras4B that inhibited potently FTase in vitro (IC 50= 500 pM)
and was highly selective for FTase over geranylgeranyltransferase I (GGTase I)(IC 50= 50 …
modification catalyzed by farnesyltransferase (FTase). Inhibitors of this enzyme have been
shown to block Ras-dependent transformation, but the mechanism by which this occurs
remains largely unknown. We have designed FTI-276, a peptide mimetic of the COOH-
terminal Cys-Val-Ile-Met of K-Ras4B that inhibited potently FTase in vitro (IC 50= 500 pM)
and was highly selective for FTase over geranylgeranyltransferase I (GGTase I)(IC 50= 50 …