Linked Life Data

21080629

Source:http://linkedlifedata.com/resource/pubmed/id/21080629

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2010-12-17
pubmed:abstractText
Reversible lysine-specific acetylation has been described as an important posttranslational modification, regulating chromatin structure and transcriptional activity in the case of core histone proteins. Histone deacetylases (HDAC) are considered as a promising target for anticancer drug development, with 2a as pan-HDAC inhibitor approved for cutanous T-cell lymphoma therapy and several other HDAC inhibitors currently in preclinical and clinical development. Protein kinases are a well-established target for cancer therapy with the EGFR/HER2 inhibitor 5 approved for treatment of advanced, HER2 positive breast cancer as a prominent example. In the present report, we present a novel strategy for cancer drug development by combination of EGFR/HER2 kinase and HDAC inhibitory activity in one molecule. By combining the structural features of 5 with an (E)-3-(aryl)-N-hydroxyacrylamide motif known from HDAC inhibitors like 1 or 3, we obtained selective inhibitors for both targets with potent cellular activity (target inhibition and cytotoxicity) of selected compounds 6a and 6c. By combining two distinct pharmacologically properties in one molecule, we postulate a broader activity spectrum and less likelihood of drug resistance in cancer patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8546-55
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Novel chimeric histone deacetylase inhibitors: a series of lapatinib hybrides as potent inhibitors of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and histone deacetylase activity.
pubmed:affiliation
Department of Pharmaceutical Chemistry I, University of Regensburg, D-93040 Regensburg, Germany. siavosh.mahboobi@chemie.uni-regensburg.de
pubmed:publicationType
Journal Article