Linked Life Data

17956279

Source:http://linkedlifedata.com/resource/pubmed/id/17956279

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 5
pubmed:dateCreated
2007-10-24
pubmed:abstractText
The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0300-5127
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1060-3
pubmed:dateRevised
2008-10-28
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
hERG channel trafficking: novel targets in drug-induced long QT syndrome.
pubmed:affiliation
Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland, OH 44109, U.S.A.
pubmed:publicationType
Journal Article, Review