PMID: 11906294Mar 22, 2002Paper

Synthesis and biological evaluation of cycloalkylidene carboxylic acids as novel effectors of Ras/Raf interaction

Journal of Medicinal Chemistry
Anke FrieseGerd Dannhardt

Abstract

The protooncogenes Ras and Raf play important roles in signal transduction pathways regulated by mitogen-activated protein kinases. Mutations of Ras that arrest the protein in its active state are frequently implicated in tumor formation. We used Ras and Raf proteins in the yeast two-hybrid system to search for natural or synthesized substances capable of modulating Ras/Raf interaction by specifically binding to one of the interacting partners. We found that cycloalkylidene carboxylic acids enhanced Ras/Raf interaction by acting on the cysteine-rich domain of Raf. Several analogues of the active substance 2-cyclohexylidene propanoic acid were synthesized and the importance of the semicyclic double bond in the stabilization of Ras/Raf interaction was demonstrated. Variation of the size and the substituents of the cyclic system as well as the length of the carboxylic acid resulted in enhanced Ras/Raf interaction.

References

Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C T ChienS Fields
Sep 1, 1990·Molecular and Cellular Biology·J S Flick, M Johnston
Aug 18, 1995·Journal of Medicinal Chemistry·J Palaty, F S Abbott
Apr 1, 1997·Current Opinion in Cell Biology·D K Morrison, R E Cutler
Apr 8, 1998·Current Opinion in Genetics & Development·J Downward
Jun 24, 1998·Biochemical and Biophysical Research Communications·D BarnardM S Marshall
Oct 20, 1998·Oncogene·C HerrmannO Müller
Oct 21, 1998·Oncogene·S L CampbellC J Der
Jul 20, 1999·Molecular and Cellular Endocrinology·M Frödin, S Gammeltoft

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Citations

Jun 22, 2013·European Journal of Medicinal Chemistry·Martina HrastStanislav Gobec
May 31, 2002·Expert Opinion on Pharmacotherapy·Walter Kolch
Jun 23, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Richard J PetroskiAllard A Cossé
Sep 23, 2010·Chemistry & Biodiversity·Thorben NawrathStefan Schulz

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