Linked Life Data

10471302

Source:http://linkedlifedata.com/resource/pubmed/id/10471302

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
1999-9-28
pubmed:abstractText
The telomere hypothesis postulates stabilization of telomere length and telomerase activation as key events in cellular immortalization and carcinogeneses. Accordingly, telomerase has been suggested as a novel and highly selective target for design of antitumor drugs. Screening of a chemical library including 16 000 synthetic compounds yielded six that strongly inhibited telomerase activity in extracts of cultured human cells, including four isothiazolone derivatives and two unrelated compounds. The most potent inhibitor was 2-[3-(trifluoromethyl)phenyl]isothiazolin-3-one (TMPI), a concentration of 1.0 microM inhibited telomerase activity by 50% according to a telomere repeat amplification protocol (TRAP) assay. Analysis using partially purified telomerase from AH7974 rat hepatoma cells demonstrated noncompetitive inhibition with the telomere-repeat primer and mixed inhibition with the dNTPs; the inhibition constant was 2.5 microM. TMPI did not inhibit eukaryotic DNA polymerase alpha, beta, or human immunodeficiency virus reverse transcriptase (HIV RT). Thus, inhibition by TMPI was highly selective for telomerase. Inhibition by TMPI was quenched by 1 mM of dithiothreitol or glutathione, suggesting that TMPI inhibits telomerase by acting at a cysteine residue. TMPI inhibition of this enzyme may find application as an antineoplastic agent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11501-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Isothiazolone derivatives selectively inhibit telomerase from human and rat cancer cells in vitro.
pubmed:affiliation
Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
pubmed:publicationType
Journal Article