Linked Life Data

17138619

Source:http://linkedlifedata.com/resource/pubmed/id/17138619

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-3-15
pubmed:abstractText
Glucocorticoid hormones exert a wide spectrum of metabolic and immunological effects. They are synthesized from a cholesterol precursor and are structurally related to the other steroid hormones, progesterone, aldosterone and oestrogen. They act through the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. The GR is an intracellular receptor; the hydrophobic ligand accesses its receptor by diffusion across the plasma membrane. The ligand-activated GR translocates to the nucleus to regulate expression of its target genes. The GR, in common with the rest of the receptor family, can be functionally divided into an N-terminal transcription activation domain, a central DNA binding domain and a C-terminal ligand binding domain, which also includes a second transactivation domain. Although synthetic glucocorticoids are the most potent anti-inflammatory agents known, their use is limited owing to the range and severity of their side-effects. The structure of the ligand binding domain of the glucocorticoid receptor has now been solved, and a series of studies has shown that even subtle changes to the ligand structure alter the final conformation of the ligand-receptor complex, with consequences for further protein recruitment and for the function of the receptor. This, coupled with the successful development of selective oestrogen receptor agonists, has led to concerted efforts to find selective GR ligands, with preserved beneficial anti-inflammatory activity, but reduced side-effect profile. Current efforts have identified several useful tool compounds, and further molecules are in development in several pharmaceutical companies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0958-0670
pubmed:author
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
299-309
pubmed:dateRevised
2007-8-13
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Modelling the glucocorticoid receptor and producing therapeutic agents with anti-inflammatory effects but reduced side-effects.
pubmed:affiliation
Endocrine Sciences Research Group, Room 3-903, Stopford Building, University of Manchester, Manchester M13 9PT, UK. david.w.ray@man.ac.uk
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't