Linked Life Data

17531323

Source:http://linkedlifedata.com/resource/pubmed/id/17531323

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-7-3
pubmed:abstractText
The CDC25 phosphatases are key regulators of cell cycle progression and play a central role in the checkpoint response to DNA damage. Their inhibition may therefore represent a promising therapeutic approach in oncology, and small molecule design strategies are currently leading to the identification of various classes of CDC25 inhibitors. Most structures developed so far are quinonoid-based compounds, but also phosphate surrogates or electrophilic entities. Considering the characteristics of the highly conserved active sites of the enzymes, many mechanisms of action have been proposed for these inhibitors. Quinonoid compounds may oxidize the catalytic site cysteine, but can also be considered as Michaël acceptors capable of reacting with the activated thiolate or other electrophilic entities. Phosphate surrogates are thought to interfere with the arginine residue, leading to reversible enzyme inhibition. But some inhibitors can combine in the same molecule several of these mechanisms, thus by fitting into the active site of the enzyme through one part of the molecule and bringing the reactive moiety in close proximity to the catalytic cysteine. This review summarizes novel classes of inhibitors that show specificity for the CDC25s over other phosphatases, cause cell proliferation inhibition and cell cycle arrest in vitro but also, for several of them, inhibition of xenografted tumoral cell growth in vivo. These promising results confirm the interest of the inhibition of CDC25 phosphatases as an anticancer therapeutic strategy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0163-7258
pubmed:author
pubmed:issnType
Print
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-12
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
What's new on CDC25 phosphatase inhibitors.
pubmed:affiliation
IPSEN Research Laboratories, Institut Henri Beaufour, 5, Avenue du Canada, F-91966 Les Ulis Cédex, France. m-odile.galcera@ipsen.com
pubmed:publicationType
Journal Article, Review