PHENOLIC REPLACEMENTS FOR CYSTEINE IN FARNESYL TRANSFERASE INHIBITORSBASED ON CVFM

Authors
KOWALCZYK JJ ACKERMANN K GARCIA AM LEWIS MD
Citation
Jj. Kowalczyk et al., PHENOLIC REPLACEMENTS FOR CYSTEINE IN FARNESYL TRANSFERASE INHIBITORSBASED ON CVFM, Bioorganic & medicinal chemistry letters, 5(24), 1995, pp. 3073-3078
Citations number
44
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
5
Issue
24
Year of publication
1995
Pages
3073 - 3078
Database
ISI
SICI code
0960-894X(1995)5:24<3073:PRFCIF>2.0.ZU;2-S
Abstract
Compounds in which cysteine of the tetrapeptide CVFM has been replaced with a phenolic benzyl substituent inhibit farnesylation of H-ras pro tein by farnesyl transferase (FTase). In the most potent inhibitors (e .g,, 5-chloro-2-hydroxybenzyl-VFM, IC50 = 0.5 mu M, approx. 8 times le ss active than CVFM) the phenolic hydroxyl is ortho to the methylene l inker. Inhibitory activity is influenced by substitution on the phenol ring.