Selective inhibition of farnesyl-protein transferase blocks ras processing in vivo.
نویسندگان
چکیده
منابع مشابه
Inhibition of farnesyl-protein transferase by gliotoxin and acetylgliotoxin.
Ras p21 proteins have been shown to be posttranslationally farnesylated on a specific carboxyterminal cysteine1 ^. Inhibition of this isoprenylation would alter membrane localization and activation of ras oncogene40. Therefore during our screening for farnesyl-protein transferase (FTase) inhibitors of microbial origin we have isolated gliotoxin (GT) and acetylgliotoxin (AGT) from the fermentati...
متن کاملCharacterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro.
R115777 [(B)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)-methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone] is a potent and selective inhibitor of farnesyl protein transferase with significant antitumor effects in vivo subsequent to oral administration in mice. In vitro, using isolated human farnesyl protein transferase, R115777 competitively inhibited the farnesylation of lamin B a...
متن کاملK- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors.
The association of mutant forms of Ras protein with a variety of human cancers has stimulated intense interest in therapies based on inhibiting oncogenic Ras signaling. Attachment of Ras proteins to the plasma membrane is required for effective Ras signaling and is initiated by the enzyme farnesyl protein transferase. We found that in the presence of potent farnesyl protein transferase inhibito...
متن کاملUbiquitin-RAS peptide extensions as substrates for farnesyl-protein transferase and carboxymethyltransferase.
Using oligonucleotide-mediated 'loop-in' mutagenesis strategies in M13, a heat-inducible ubiquitin (Ub) gene was extended by sequences coding for the C-terminal 11 amino acids of Ha-RAS. The resulting gene was transformed into AR13 and production of the Ub-peptide extension was induced by heat treatment. After one-step purification, the fusion protein (Ub-cRAS) was used as a substrate for farne...
متن کاملPharmacokinetics and metabolism of a RAS farnesyl transferase inhibitor in rats and dogs: in vitro-in vivo correlation.
Compound I (1-(3-chlorophenyl)-4-[(1-(4-cyanobenzyl)-1H-imidazol-5-yl)methyl]piperazin-2-one) is a potent and selective inhibitor of farnesyl-protein transferase (FPTase). The pharmacokinetics and metabolism of compound I displayed species differences in rats and dogs. After oral administration, the drug was well absorbed in dogs but less so in rats. Following i.v. administration, compound I wa...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 1993
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(18)52998-7