PMID: 9545527Apr 18, 1998Paper

Stringent structural requirements for anti-Ras activity of S-prenyl analogues

Biochimica Et Biophysica Acta
Z AharonsonY Kloog

Abstract

The carboxy terminal S-farnesylcysteine of Ras oncoproteins is required for their membrane anchorage and transforming activities. We showed previously that S-farnesylthiosalicylic acid (FTS) affects the membrane anchorage of activated H-Ras in EJ cells and inhibits their growth. We report here on structural elements in S-prenyl derivatives that specifically inhibit the growth of EJ cells, but not of untransformed Rat-1 cells. Inhibition of the Ras-dependent extracellular signal-regulated protein kinase (ERK), of DNA synthesis and of EJ cell growth were apparent after treatment with FTS or its 5-fluoro, 5-chloro and 4-fluoro derivatives or with the C20 S-geranylgeranyl derivative of thiosalicylic acid. The 4-Cl-FTS analogue was a weak inhibitor of EJ cell growth. The 3-Cl-FTS analogue and the FTS carboxyl methyl ester were inactive, as were the C10 S-geranyl derivative of thiosalicylic acid, farnesoic acid, N-acetyl-S-farnesyl-L-cysteine and S-farne-sylthiopropionic acid. The structural requirements for anti-Ras activity of S-prenyl analogues thus appear to be rather stringent. With regard to chain length, the C15 farnesyl group linked to a rigid backbone seems to be necessary and sufficient. A free carboxyl group in an appropri...Continue Reading

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Citations

Oct 3, 2007·Cancer Chemotherapy and Pharmacology·Roni HaklaiYoel Kloog
Apr 16, 2013·Cancer Metastasis Reviews·Yabin ChengGang Li
Dec 4, 2003·Pharmacology, Biochemistry, and Behavior·Nazarius S LamangoClivel G Charlton
Apr 28, 1999·Bioorganic & Medicinal Chemistry·F EiseleH Waldmann
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·B JansenK Wolff
Jun 5, 2012·Genes & Development·Hensin TsaoDavid E Fisher
Oct 4, 2011·Trends in Molecular Medicine·Zhenyu JiHensin Tsao
Jan 22, 2003·The Journal of Investigative Dermatology·Julius Halaschek-WienerBurkhard Jansen
Oct 16, 2012·Journal of Biomedical Materials Research. Part a·Amir KraitzerMeital Zilberman
Jan 5, 2001·Expert Opinion on Investigational Drugs·Y KloogM Sinensky
Apr 29, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Avijit RayBonnie N Dittel
Dec 26, 2013·Oncotarget·Eran SchmuklerRonit Pinkas-Kramarski
Feb 2, 2013·Oncotarget·Eran SchmuklerRonit Pinkas-Kramarski
Dec 6, 2019·MedChemComm·Exequiel O J PortaGuillermo R Labadie
Jun 10, 2017·Scientific Reports·Jorge LevicanOscar León
Mar 28, 2003·Journal of the American Society of Nephrology : JASN·Helen C ClarkeBruce M Hendry
Aug 14, 1999·Biochimica Et Biophysica Acta·D Tisch-IdelsonI Aviram
Dec 11, 1999·Biochimica Et Biophysica Acta·G EladY Kloog

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