Linked Life Data

16314690

Source:http://linkedlifedata.com/resource/pubmed/id/16314690

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-12-20
pubmed:abstractText
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcriptional factor implicated in regulating adipogenesis, glucose homeostasis, and in mediating the action of the insulin sensitizing anti-diabetic thiazolidinedione (TZD) compounds. [3-(2,4-Dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3-H-benzimidazole-5-carboxamide] (FK614) is a structurally novel PPARgamma agonist that demonstrates potent anti-diabetic activity in vivo. Herein, we describe that FK614 is a selective PPARgamma ligand with specific transactivation properties that are dependent upon the context of coactivators. FK614 dissociates the corepressors NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoid and thyroid hormone receptors) from PPARgamma as effectively as rosiglitazone and pioglitazone, but can also differentially induce a ligand specific interaction of PPARgamma with coactivators. The amount of CBP (CREB-binding protein) and SRC-1 (steroid receptor coactivator-1) recruited by FK614 was less than that induced by rosiglitazone and pioglitazone, but FK614 caused similar PGC-1alpha (PPARgamma coactivator-1alpha) recruitment as these compounds. As a consequence of these ligand-specific differences in the strength of ligand-type specific interactions of PPARgamma and coactivators, FK614 functions as a partial or full agonist for transcriptional activation depending upon the amount of specific coactivators in cells following overexpression. In conclusion, FK614 is a novel, non-TZD type, and selective PPARgamma modulator whose pharmacological properties are distinct from rosiglitazone and pioglitazone.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3-(2,4-dichlorobenzyl)-2-methyl-N-(p..., http://linkedlifedata.com/resource/pubmed/chemical/Benzimidazoles, http://linkedlifedata.com/resource/pubmed/chemical/CREB-Binding Protein, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione, http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Ligands, http://linkedlifedata.com/resource/pubmed/chemical/NCOA1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 1, http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma, http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/pioglitazone, http://linkedlifedata.com/resource/pubmed/chemical/rosiglitazone
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1347-8613
pubmed:author
pubmed:issnType
Print
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
342-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
FK614, a novel peroxisome proliferator-activated receptor gamma modulator, induces differential transactivation through a unique ligand-specific interaction with transcriptional coactivators.
pubmed:affiliation
Pharmacology Research Laboratories, Astellas Pharma Inc, Japan.
pubmed:publicationType
Journal Article