Linked Life Data

7700260

Source:http://linkedlifedata.com/resource/pubmed/id/7700260

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-4-28
pubmed:abstractText
The co-transfection assay is a novel functional assay using cells transiently transfected with plasmids encoding intracellular receptors and corresponding reporter genes. Using this assay, natural product extracts were tested to identify compounds that modulate intracellular receptor activity, measured as changes in reporter gene activity. A crude extract of the marine alga Cymopolia barbata was found to inhibit progesterone-stimulated reporter gene expression in cells transfected with the human progesterone receptor (hPR) and an appropriate reporter construct. Purification of the active constituents of the extract, guided by the co-transfection assay, yielded two diastereomers of cyclocymopol monomethyl ether, possessing opposing pharmacological activities with the hPR. The antagonist (3R)-cyclocymopol monomethyl ether (LG100127) blocked 1 nM progesterone-stimulated reporter gene expression with an IC50 value of 549 +/- 55 nM in the co-transfection assay. The agonist (3S)-cyclocymopol monomethyl ether (LG100128) had efficacy similar to that of progesterone and an EC50 value of 35 +/- 2 nM. Stimulation by progesterone of the hPR in the human breast cancer cell line T-47D results in enhanced expression of alkaline phosphatase; LG100127 blocked alkaline phosphatase expression stimulated either by progesterone or by LG100128, and LG100128 mimicked progesterone in this assay. Both diastereomers displaced [3H]progesterone from baculovirus-expressed hPR. LG100127 and LG100128 each interacted with the human androgen receptor but did not interact with the human glucocorticoid receptor, estrogen receptor, vitamin D receptor, or retinoid receptors. In summary, these in vitro studies describe the first nonsteroidal pharmacophores for the hPR and demonstrate the use of the co-transfection assay in their discovery.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
630-5
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Nonsteroidal human progesterone receptor modulators from the marine alga Cymopolia barbata.
pubmed:affiliation
Ligand Pharmaceuticals Inc., San Diego, California 92121.
pubmed:publicationType
Journal Article