Linked Life Data

16787319

Source:http://linkedlifedata.com/resource/pubmed/id/16787319

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-6-21
pubmed:abstractText
Aberrant signalling through the pathways of small GTP-binding proteins, belonging to the Ras superfamily (Ras, Rho, Rac, Cdc42 etc.), occurs in several types of cancer, where mutated Ras accumulates in its GTP-bound active form and causes uncontrolled cell proliferation. For these reasons, molecules able to target the Ras pathway in any of its stages are potentially useful in anti-cancer therapies. Inhibition of farnesyl-protein transferase (FTase), the enzyme that post-translationally activates Ras, has been pursued for the obvious role of the Ras oncoprotein in human malignancies. It was later found that some mutated forms of Ras (K- and N-Ras) can also be geranylgeranylated by geranylgeranyl-protein transferase (GGTase) when FTase is blocked, circumventing the antiproliferative effects of FTase inhibitors. Therefore, a new task has been the search for new GGTase inhibitors, which can also interfere on cell proliferation by blocking the isoprenylation of other Ras superfamily proteins (i.e. Rho, Rac, Cdc42) involved in the regulation of cell cycle progression. We have recently described a series of phosphonoacetamido- and phosphonoacetamidoxy-stable analogues of geranylgeranyl-diphosphate (GGdP) possessing good GGTase inhibitory properties and, some of them, also remarkable GGTase/FTase selectivity levels. We have now extended this series to a larger number of variously substituted phosphonoacetamidoxy-analogues of GGdP in order to establish the effect on GGTase inhibitory activity and selectivity due to the presence of different substituents in the polar portion of these GGdP mimics. We have also measured the cytotoxicity of these compounds on tumour cell lines with the aim of evaluating their potential anti-proliferative effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1573-4064
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
239-44
pubmed:dateRevised
2008-9-20
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Variously substituted (phosphonoacetamido)oxy analogues of geranylgeranyl diphosphate (GGdP) as GGdP-transferase (GGTase) inhibitors and antiproliferative agents.
pubmed:affiliation
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
pubmed:publicationType
Journal Article