Constrained phytoestrogens and analogues as ERbeta selective ligands.
A new series of ERbeta (ERbeta) selective ligands has been prepared. One of the compounds 6, structurally related to the phytoestrogen apigenin 4, displays a binding preference for ERbeta over ERalpha of over 40-fold. In addition to its binding selectivity, 6 was able to potently induce metallothionein (an ERbeta specific response in human SAOS-2 cells) while demonstrating low potency in an ERalpha dependant ERE-tk luciferase assay in MCF-7 cells. Such receptor and cell selectivity could make 6 a useful molecular probe for better understanding the role of ERbeta in mammalian physiology.
Miller
Chris P
CP
Chemical Sciences, Wyeth Research, 500 Arcola Road, PA 19426, Collegeville, USA.
Collini
Michael D
MD
Harris
Heather A
HA
D000478:Alkylation; D047310:Apigenin; D002460:Cell Line; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D019833:Genistein / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007529:Isoflavones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008156:Luciferases / Q000235:genetics; D008668:Metallothionein / Q000096:biosynthesis; D048789:Phytoestrogens; D028321:Plant Preparations / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005419:Flavonoids; D007202:Indicators and Reagents; D007529:Isoflavones; D008024:Ligands; D048789:Phytoestrogens; D028321:Plant Preparations; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D047310:Apigenin; D008668:Metallothionein; D019833:Genistein; D008156:Luciferases