Linked Life Data

10786665

Source:http://linkedlifedata.com/resource/pubmed/id/10786665

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-5-11
pubmed:abstractText
Geldanamycin (GM) is a natural antibiotic that binds Hsp90 and induces the degradation of receptor tyrosine kinases, steroid receptors, and Raf. It is a potent inhibitor of cancer cells that overexpress HER-kinases, but its effects on other important proteins may cause significant toxicity and limit its clinical use. We report the synthesis and identification of a GM dimer, GMD-4c, which had selective activity against HER-kinases. Selectivity was a function of linker length and required two intact GM moieties. GMD-4c is a potent inducer of G1 block and apoptosis of breast cancer cell lines that overexpress HER2, but does not appreciably inhibit the growth of 32D cells that lack HER-kinases. GMD-4c could be useful in the treatment of carcinomas dependent on HER-kinases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2090-4
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10786665-Antibiotics, Antineoplastic, pubmed-meshheading:10786665-Benzoquinones, pubmed-meshheading:10786665-Blotting, Western, pubmed-meshheading:10786665-Breast Neoplasms, pubmed-meshheading:10786665-Cell Division, pubmed-meshheading:10786665-Dimerization, pubmed-meshheading:10786665-Down-Regulation, pubmed-meshheading:10786665-Humans, pubmed-meshheading:10786665-Immunohistochemistry, pubmed-meshheading:10786665-Inhibitory Concentration 50, pubmed-meshheading:10786665-Lactams, Macrocyclic, pubmed-meshheading:10786665-Proto-Oncogene Proteins c-raf, pubmed-meshheading:10786665-Quinones, pubmed-meshheading:10786665-Receptor, IGF Type 1, pubmed-meshheading:10786665-Receptor, erbB-2, pubmed-meshheading:10786665-Receptors, Estrogen, pubmed-meshheading:10786665-Substrate Specificity, pubmed-meshheading:10786665-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases.
pubmed:affiliation
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. zhengf@mskcc.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't